@article{rahman_zhou_deiters_haugh_2023, title={Dissection of MKK6 and p38 Signaling Using Light-Activated Protein Kinases}, volume={11}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.202300551}, abstractNote={Abstract}, journal={CHEMBIOCHEM}, author={Rahman, Shah Md. Toufiqur and Zhou, Wenyuan and Deiters, Alexander and Haugh, Jason M.}, year={2023}, month={Nov} }
 @article{zhou_ryan_janosko_shoger_haugh_gottschalk_deiters_2023, title={Isoform-specific optical activation of kinase function reveals p38-ERK signaling crosstalk}, volume={8}, ISSN={["2633-0679"]}, DOI={10.1039/d2cb00157}, journal={RSC CHEMICAL BIOLOGY}, author={Zhou, Wenyuan and Ryan, Amy and Janosko, Chasity P. and Shoger, Karsen E. and Haugh, Jason M. and Gottschalk, Rachel A. and Deiters, Alexander}, year={2023}, month={Aug} }
 @article{emanuelson_ankenbruck_kumbhare_thomas_connelly_baktash_randall_deiters_2022, title={Transcriptional Inhibition of MicroRNA miR-122 by Small Molecules Reduces Hepatitis C Virus Replication in Liver Cells}, ISSN={["1520-4804"]}, DOI={10.1021/acs.jmedchem.2c01141}, abstractNote={MicroRNAs (miRNAs) are noncoding RNA molecules of 22-24 nucleotides that are estimated to regulate thousands of genes in humans, and their dysregulation has been implicated in many diseases. MicroRNA-122 (miR-122) is the most abundant miRNA in the liver and has been linked to the development of hepatocellular carcinoma and hepatitis C virus (HCV) infection. Its role in these diseases renders miR-122 a potential target for small-molecule therapeutics. Here, we report the discovery of a new sulfonamide class of small-molecule miR-122 inhibitors from a high-throughput screen using a luciferase-based reporter assay. Structure-activity relationship (SAR) studies and secondary assays led to the development of potent and selective miR-122 inhibitors. Preliminary mechanism-of-action studies suggest a role in the promoter-specific transcriptional inhibition of miR-122 expression through direct binding to the liver-enriched transcription factor hepatocyte nuclear factor 4α. Importantly, the developed inhibitors significantly reduce HCV replication in human liver cells.}, journal={JOURNAL OF MEDICINAL CHEMISTRY}, author={Emanuelson, Cole and Ankenbruck, Nicholas and Kumbhare, Rohan and Thomas, Meryl and Connelly, Colleen and Baktash, Yasmine and Randall, Glenn and Deiters, Alexander}, year={2022}, month={Nov} }
 @article{rahman_zhou_deiters_haugh_2020, title={Optical control of MAP kinase kinase 6 (MKK6) reveals that it has divergent roles in pro-apoptotic and anti-proliferative signaling}, volume={295}, ISSN={["1083-351X"]}, DOI={10.1074/jbc.RA119.012079}, abstractNote={The selective pressure imposed by extrinsic death signals and stressors adds to the challenge of isolating and interpreting the roles of proteins in stress-activated signaling networks. By expressing a kinase with activating mutations and a caged lysine blocking the active site, we can rapidly switch on catalytic activity with light and monitor the ensuing dynamics. Applying this approach to MAP kinase 6 (MKK6), which activates the p38 subfamily of MAPKs, we found that decaging active MKK6 in fibroblasts is sufficient to trigger apoptosis in a p38-dependent manner. Both in fibroblasts and in a murine melanoma cell line expressing mutant B-Raf, MKK6 activation rapidly and potently inhibited the pro-proliferative extracellular signal–regulated kinase (ERK) pathway; to our surprise, this negative cross-regulation was equally robust when all p38 isoforms were inhibited. These results position MKK6 as a new pleiotropic signal transducer that promotes both pro-apoptotic and anti-proliferative signaling, and they highlight the utility of caged, light-activated kinases for dissecting stress-activated signaling networks.}, number={25}, journal={JOURNAL OF BIOLOGICAL CHEMISTRY}, author={Rahman, Shah Md. Toufiqur and Zhou, Wenyuan and Deiters, Alexander and Haugh, Jason M.}, year={2020}, month={Jun}, pages={8494–8504} }
 @article{enamorado_connelly_deiters_comins_2015, title={A concise synthesis of the Lycopodium alkaloid cermizine D}, volume={56}, ISSN={["0040-4039"]}, DOI={10.1016/j.tetlet.2015.04.013}, abstractNote={A racemic and asymmetric synthesis of cermizine D (1) was accomplished in six steps from 4-methoxypyridine or 4-methoxy-3-TIPS-pyridine in 12% and 13% overall yield, respectively. A key step is a stereoselective 1,4-addition of a 2-((trimethylsilyl)methyl)pyridine-derived cuprate to a bicyclic 2,3-dihydro-4-pyridone. Racemic and (−)-cermizine D failed to exhibit cytotoxicity against four different cell lines.}, number={23}, journal={TETRAHEDRON LETTERS}, author={Enamorado, Monica F. and Connelly, Colleen M. and Deiters, Alexander and Comins, Daniel L.}, year={2015}, month={Jun}, pages={3683–3685} }
 @article{hemphill_liu_uprety_samanta_tsang_juliano_deiters_2015, title={Conditional Control of Alternative Splicing through Light-Triggered Splice-Switching Oligonucleotides}, volume={137}, ISSN={["0002-7863"]}, DOI={10.1021/jacs.5b00580}, abstractNote={The spliceosome machinery is composed of several proteins and multiple small RNA molecules that are involved in gene regulation through the removal of introns from pre-mRNAs in order to assemble exon-based mRNA containing protein-coding sequences. Splice-switching oligonucleotides (SSOs) are genetic control elements that can be used to specifically control the expression of genes through correction of aberrant splicing pathways. A current limitation with SSO methodologies is the inability to achieve conditional control of their function paired with high spatial and temporal resolution. We addressed this limitation through site-specific installation of light-removable nucleobase-caging groups as well as photocleavable backbone linkers into synthetic SSOs. This enables optochemical OFF → ON and ON → OFF switching of their activity and thus precise control of alternative splicing. The use of light as a regulatory element allows for tight spatial and temporal control of splice switching in mammalian cells and animals.}, number={10}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Hemphill, James and Liu, Qingyang and Uprety, Rajendra and Samanta, Subhas and Tsang, Michael and Juliano, Rudolph L. and Deiters, Alexander}, year={2015}, month={Mar}, pages={3656–3662} }
 @article{brown_zou_shirvanyants_zhang_samanta_mantravadi_dokholyan_deiters_2015, title={Light-cleavable rapamycin dimer as an optical trigger for protein dimerization}, volume={51}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc09442e}, abstractNote={Protein heterodimerization of FKBP12 and FRB can be optically controlled with a photocleavable rapamycin dimer.}, number={26}, journal={CHEMICAL COMMUNICATIONS}, author={Brown, Kalyn A. and Zou, Yan and Shirvanyants, David and Zhang, Jie and Samanta, Subhas and Mantravadi, Pavan K. and Dokholyan, Nikolay V. and Deiters, Alexander}, year={2015}, pages={5702–5705} }
 @article{govan_young_lively_deiters_2015, title={Optically triggered immune response through photocaged oligonucleotides}, volume={56}, ISSN={["0040-4039"]}, DOI={10.1016/j.tetlet.2015.01.165}, abstractNote={Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6.}, number={23}, journal={TETRAHEDRON LETTERS}, author={Govan, Jeane M. and Young, Douglas D. and Lively, Mark O. and Deiters, Alexander}, year={2015}, month={Jun}, pages={3639–3642} }
 @article{engelke_chou_uprety_jess_deiters_2014, title={Control of Protein Function through Optochemical Translocation}, volume={3}, ISSN={["2161-5063"]}, DOI={10.1021/sb400192a}, abstractNote={Controlled manipulation of proteins and their function is important in almost all biological disciplines. Here, we demonstrate control of protein activity with light. We present two different applications—light-triggered transcription and light-triggered protease cleavage—both based on the same concept of protein mislocation, followed by optochemically triggered translocation to an active cellular compartment. In our approach, we genetically encode a photocaged lysine into the nuclear localization signal (NLS) of the transcription factor SATB1. This blocks nuclear import of the protein until illumination induces caging group removal and release of the protein into the nucleus. In the first application, prepending this NLS to the transcription factor FOXO3 allows us to optochemically switch on its transcription activity. The second application uses the developed light-activated NLS to control nuclear import of TEV protease and subsequent cleavage of nuclear proteins containing TEV cleavage sites. The small size of the light-controlled NLS (only 20 amino acids) minimizes impact of its insertion on protein function and promises a general approach to a wide range of optochemical applications. Since the light-activated NLS is genetically encoded and optically triggered, it will prove useful to address a variety of problems requiring spatial and temporal control of protein function, for example, in stem-cell, developmental, and cancer biology.}, number={10}, journal={ACS SYNTHETIC BIOLOGY}, author={Engelke, Hanna and Chou, Chungjung and Uprety, Rajendra and Jess, Phillip and Deiters, Alexander}, year={2014}, month={Oct}, pages={731–736} }
 @article{uprety_luo_liu_naro_samanta_deiters_2014, title={Genetic Encoding of Caged Cysteine and Caged Homocysteine in Bacterial and Mammalian Cells}, volume={15}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.201400073}, abstractNote={Abstract}, number={12}, journal={CHEMBIOCHEM}, author={Uprety, Rajendra and Luo, Ji and Liu, Jihe and Naro, Yuta and Samanta, Subhas and Deiters, Alexander}, year={2014}, month={Aug}, pages={1793–1799} }
 @article{lee_kurra_yang_torres-kolbus_deiters_liu_2014, title={Genetically encoded unstrained olefins for live cell labeling with tetrazine dyes}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc06435f}, abstractNote={A number of non-canonical amino acids (NCAAs) with unstrained olefins are genetically encoded using mutant pyrrolysyl-tRNA synthetase–tRNAPylCUA pairs for catalyst-free labeling with tetrazine dyes.}, number={86}, journal={CHEMICAL COMMUNICATIONS}, author={Lee, Yan-Jiun and Kurra, Yadagiri and Yang, Yanyan and Torres-Kolbus, Jessica and Deiters, Alexander and Liu, Wenshe R.}, year={2014}, pages={13085–13088} }
 @article{lee_kurra_yang_torres-kolbus_deiters_liu_2014, title={Genetically encoded unstrained olefins for live cell labeling with tetrazine dyes (vol 50, pg 13085, 2014)}, volume={50}, ISSN={["1364-548X"]}, DOI={10.1039/c4cc90401j}, abstractNote={Correction for ‘Genetically encoded unstrained olefins for live cell labeling with tetrazine dyes’ by Yan-Jiun Lee et al., Chem. Commun., 2014, DOI: 10.1039/c4cc06435f.}, number={87}, journal={CHEMICAL COMMUNICATIONS}, author={Lee, Yan-Jiun and Kurra, Yadagiri and Yang, Yanyan and Torres-Kolbus, Jessica and Deiters, Alexander and Liu, Wenshe R.}, year={2014}, month={Nov}, pages={13396–13396} }
 @article{walsh_gardner_deiters_williams_2014, title={Intracellular Light-Activation of Riboswitch Activity}, volume={15}, ISSN={1439-4227}, url={http://dx.doi.org/10.1002/cbic.201400024}, DOI={10.1002/cbic.201400024}, abstractNote={Abstract}, number={9}, journal={ChemBioChem}, publisher={Wiley}, author={Walsh, Steven and Gardner, Laura and Deiters, Alexander and Williams, Gavin J.}, year={2014}, month={May}, pages={1346–1351} }
 @article{volvert_prevot_close_laguesse_pirotte_hemphill_rogister_kruzy_sacheli_moonen_et al._2014, title={MicroRNA Targeting of CoREST Controls Polarization of Migrating Cortical Neurons}, volume={7}, ISSN={["2211-1247"]}, DOI={10.1016/j.celrep.2014.03.075}, abstractNote={The migration of cortical projection neurons is a multistep process characterized by dynamic cell shape remodeling. The molecular basis of these changes remains elusive, and the present work describes how microRNAs (miRNAs) control neuronal polarization during radial migration. We show that miR-22 and miR-124 are expressed in the cortical wall where they target components of the CoREST/REST transcriptional repressor complex, thereby regulating doublecortin transcription in migrating neurons. This molecular pathway underlies radial migration by promoting dynamic multipolar-bipolar cell conversion at early phases of migration, and later stabilization of cell polarity to support locomotion on radial glia fibers. Thus, our work emphasizes key roles of some miRNAs that control radial migration during cerebral corticogenesis.}, number={4}, journal={CELL REPORTS}, author={Volvert, Marie-Laure and Prevot, Pierre-Paul and Close, Pierre and Laguesse, Sophie and Pirotte, Sophie and Hemphill, James and Rogister, Florence and Kruzy, Nathalie and Sacheli, Rosalie and Moonen, Gustave and et al.}, year={2014}, month={May}, pages={1168–1183} }
 @misc{liu_deiters_2014, title={Optochemical Control of Deoxyoligonucleotide Function via a Nucleobase-Caging Approach}, volume={47}, ISSN={["1520-4898"]}, DOI={10.1021/ar400036a}, abstractNote={Synthetic oligonucleotides have been extensively applied tocontrol a wide range of biological processes such as gene expression, gene repair, DNA replication, and protein activity. Based on well-established sequence design rules that typically rely on Watson-Crick base pairing interactions researchers can readily program the function of these oligonucleotides. Therefore oligonucleotides provide a flexible platform for targeting a wide range of biological molecules, including DNA, RNA, and proteins. In addition, oligonucleotides are commonly used research tools in cell biology and developmental biology. However, a lack of conditional control methods has hampered the precise spatial and temporal regulation of oligonucleotide activity, which limits the application of these reagents to investigate complex biological questions. Nature controls biological function with a high level of spatial and temporal resolution and in order to elucidate the molecular mechanisms of biological processes, researchers need tools that allow for the perturbation of these processes with Nature's precision. Light represents an excellent external regulatory element since irradiation can be easily controlled spatially and temporally. Thus, researchers have developed several different methods to conditionally control oligonucleotide activity with light. One of the most versatile strategies is optochemical regulation through the installation and removal of photolabile caging groups on oligonucleotides. To produce switches that can control nucleic acid function with light, chemists introduce caging groups into the oligomer backbone or on specific nucleobases to block oligonucleotide function until the caging groups are removed by light exposure. In this Account, we focus on the application of caged nucleobases to the photoregulation of DNA function. Using this approach, we have both activated and deactivated gene expression optochemically at the transcriptional and translational level with spatial and temporal control. Specifically, we have used caged triplex-forming oligomers and DNA decoys to regulate transcription, and we have regulated translation with light-activated antisense agents. Moreover, we also discuss strategies that can trigger DNA enzymatic activity, DNA amplification, and DNA mutagenesis by light illumination. More recently, we have developed light-activated DNA logic operations, an advance that may lay the foundation for the optochemical control of complex DNA calculations.}, number={1}, journal={ACCOUNTS OF CHEMICAL RESEARCH}, author={Liu, Qingyang and Deiters, Alexander}, year={2014}, month={Jan}, pages={45–55} }
 @article{hemphill_govan_uprety_tsang_deiters_2014, title={Site-Specific Promoter Caging Enables Optochemical Gene Activation in Cells and Animals}, volume={136}, ISSN={["1520-5126"]}, DOI={10.1021/ja500327g}, abstractNote={In cell and molecular biology, double-stranded circular DNA constructs, known as plasmids, are extensively used to express a gene of interest. These gene expression systems rely on a specific promoter region to drive the transcription of genes either constitutively (i.e., in a continually “ON” state) or conditionally (i.e., in response to a specific transcription initiator). However, controlling plasmid-based expression with high spatial and temporal resolution in cellular environments and in multicellular organisms remains challenging. To overcome this limitation, we have site-specifically installed nucleobase-caging groups within a plasmid promoter region to enable optochemical control of transcription and, thus, gene expression, via photolysis of the caging groups. Through the light-responsive modification of plasmid-based gene expression systems, we have demonstrated optochemical activation of an exogenous fluorescent reporter gene in both tissue culture and a live animal model, as well as light-induced overexpression of an endogenous signaling protein.}, number={19}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Hemphill, James and Govan, Jeane and Uprety, Rajendra and Tsang, Michael and Deiters, Alexander}, year={2014}, month={May}, pages={7152–7158} }
 @article{torres-kolbus_chou_liu_deiters_2014, title={Synthesis of Non-linear Protein Dimers through a Genetically Encoded Thiol-ene Reaction}, volume={9}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0105467}, abstractNote={Site-specific incorporation of bioorthogonal unnatural amino acids into proteins provides a useful tool for the installation of specific functionalities that will allow for the labeling of proteins with virtually any probe. We demonstrate the genetic encoding of a set of alkene lysines using the orthogonal PylRS/PylTCUA pair in Escherichia coli. The installed double bond functionality was then applied in a photoinitiated thiol-ene reaction of the protein with a fluorescent thiol-bearing probe, as well as a cysteine residue of a second protein, showing the applicability of this approach in the formation of heterogeneous non-linear fused proteins.}, number={9}, journal={PLOS ONE}, author={Torres-Kolbus, Jessica and Chou, Chungjung and Liu, Jihe and Deiters, Alexander}, year={2014}, month={Sep} }
 @article{vonlanthen_connelly_deiters_linden_finney_2014, title={Thiourea-Based Fluorescent Chemosensors for Aqueous Metal Ion Detection and Cellular Imaging}, volume={79}, ISSN={["1520-6904"]}, DOI={10.1021/jo500710g}, abstractNote={We describe three significant advances in the use of thioureas as reporting elements for metal-responsive fluorescent chemosensors. First, on the basis of the crystal structure of a chemosensor analogue, we provide a deeper understanding of the details of the thiourea coordination environment. Second, we describe a new generation of chemosensors with higher affinities for Zn(2+) and Cd(2+) than were observed for earlier probes, expanding the scope of this type of probe beyond Hg(2+) detection. Third, we show that a thiourea-based chemosensor can be employed for fluorescence microscopy imaging of Hg(2+) ion concentrations in living mammalian cells.}, number={13}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Vonlanthen, Mireille and Connelly, Colleen M. and Deiters, Alexander and Linden, Anthony and Finney, Nathaniel S.}, year={2014}, month={Jul}, pages={6054–6060} }
 @article{kurra_odoi_lee_yang_lu_wheeler_torres-kolbus_deiters_liu_2014, title={Two Rapid Catalyst-Free Click Reactions for In Vivo Protein Labeling of Genetically Encoded Strained Alkene/Alkyne Functionalities}, volume={25}, ISSN={["1043-1802"]}, DOI={10.1021/bc500361d}, abstractNote={Detailed kinetic analyses of inverse electron-demand Diels–Alder cycloaddition and nitrilimine-alkene/alkyne 1,3-diploar cycloaddition reactions were conducted and the reactions were applied for rapid protein bioconjugation. When reacted with a tetrazine or a diaryl nitrilimine, strained alkene/alkyne entities including norbornene, trans-cyclooctene, and cyclooctyne displayed rapid kinetics. To apply these “click” reactions for site-specific protein labeling, five tyrosine derivatives that contain a norbornene, trans-cyclooctene, or cyclooctyne entity were genetically encoded into proteins in Escherichia coli using an engineered pyrrolysyl-tRNA synthetase-tRNACUAPyl pair. Proteins bearing these noncanonical amino acids were successively labeled with a fluorescein tetrazine dye and a diaryl nitrilimine both in vitro and in living cells.}, number={9}, journal={BIOCONJUGATE CHEMISTRY}, author={Kurra, Yadagiri and Odoi, Keturah A. and Lee, Yan-Jiun and Yang, Yanyan and Lu, Tongxiang and Wheeler, Steven E. and Torres-Kolbus, Jessica and Deiters, Alexander and Liu, Wenshe R.}, year={2014}, month={Sep}, pages={1730–1738} }
 @article{govan_uprety_thomas_lusic_lively_deiters_2013, title={Cellular Delivery and Photochemical Activation of Antisense Agents through a Nucleobase Caging Strategy}, volume={8}, ISSN={["1554-8937"]}, DOI={10.1021/cb400293e}, abstractNote={Antisense oligonucleotides are powerful tools to regulate gene expression in cells and model organisms. However, a transfection or microinjection is typically needed for efficient delivery of the antisense agent. We report the conjugation of multiple HIV TAT peptides to a hairpin-protected antisense agent through a light-cleavable nucleobase caging group. This conjugation allows for the facile delivery of the antisense agent without a transfection reagent, and photochemical activation offers precise control over gene expression. The developed approach is highly modular, as demonstrated by the conjugation of folic acid to the caged antisense agent. This enabled targeted cell delivery through cell-surface folate receptors followed by photochemical triggering of antisense activity. Importantly, the presented strategy delivers native oligonucleotides after light-activation, devoid of any delivery functionalities or modifications that could otherwise impair their antisense activity.}, number={10}, journal={ACS CHEMICAL BIOLOGY}, author={Govan, Jeane M. and Uprety, Rajendra and Thomas, Meryl and Lusic, Hrvoje and Lively, Mark O. and Deiters, Alexander}, year={2013}, month={Oct}, pages={2272–2282} }
 @article{hemphill_deiters_2013, title={DNA Computation in Mammalian Cells: MicroRNA Logic Operations}, volume={135}, ISSN={["0002-7863"]}, DOI={10.1021/ja404350s}, abstractNote={DNA computation can utilize logic gates as modules to create molecular computers with biological inputs. Modular circuits that recognize nucleic acid inputs through strand hybridization activate computation cascades to produce controlled outputs. This allows for the construction of synthetic circuits that can be interfaced with cellular environments. We have engineered oligonucleotide AND gates to respond to specific microRNA (miRNA) inputs in live mammalian cells. Both single and dual-sensing miRNA-based computation devices were synthesized for the cell-specific identification of endogenous miR-21 and miR-122. A logic gate response was observed with miRNA expression regulators, exhibiting molecular recognition of miRNA profile changes. Nucleic acid logic gates that are functional in a cellular environment and recognize endogenous inputs significantly expand the potential of DNA computation to monitor, image, and respond to cell-specific markers.}, number={28}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Hemphill, James and Deiters, Alexander}, year={2013}, month={Jul}, pages={10512–10518} }
 @article{hemphill_chou_chin_deiters_2013, title={Genetically encoded light-activated transcription for spatiotemporal control of gene expression and gene silencing in mammalian cells}, volume={135}, DOI={10.1021/ja4051026}, abstractNote={Photocaging provides a method to spatially and temporally control biological function and gene expression with high resolution. Proteins can be photochemically controlled through the site-specific installation of caging groups on amino acid side chains that are essential for protein function. The photocaging of a synthetic gene network using unnatural amino acid mutagenesis in mammalian cells was demonstrated with an engineered bacteriophage RNA polymerase. A caged T7 RNA polymerase was expressed in cells with an expanded genetic code and used in the photochemical activation of genes under control of an orthogonal T7 promoter, demonstrating tight spatial and temporal control. The synthetic gene expression system was validated with two reporter genes (luciferase and EGFP) and applied to the light-triggered transcription of short hairpin RNA constructs for the induction of RNA interference.}, number={36}, journal={Journal of the American Chemical Society}, author={Hemphill, J. and Chou, C. J. and Chin, J. W. and Deiters, A.}, year={2013}, pages={13433–13439} }
 @article{thomas_deiters_2013, title={MicroRNA miR-122 as a therapeutic target for oligonucleotides and small molecules}, volume={20}, DOI={10.2174/0929867311320290009}, abstractNote={The most abundant microRNA (miRNA) in the liver, miR-122, is regulated by specific, liver-enriched transcription factors and is responsible for proper proliferation and differentiation of hepatocytes and for the regulation of lipid and cholesterol metabolisms. miR-122 is also involved in several hepatic disorders, as downregulation of miR-122 is often associated with hepatocellular carcinoma (HCC) and miR-122 is a required component for the replication and proliferation of the hepatitis C virus (HCV). Various probes have been developed to promote a better understanding of the involvement of miR-122 in liver diseases, including modified antisense agents and small molecule inhibitors. These agents, capable of specifically modifying miR-122 activity, provide excellent tools to investigate the function and regulation of miR-122 and offer potential new lead compounds for drug discovery. Especially small molecule modifiers can display numerous advantages over nucleotide analogs, as discussed in this review.}, number={29}, journal={Current Medicinal Chemistry}, author={Thomas, M. and Deiters, A.}, year={2013}, pages={3629–3640} }
 @article{govan_young_lusic_liu_lively_deiters_2013, title={Optochemical control of RNA interference in mammalian cells}, volume={41}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkt806}, abstractNote={Short interfering RNAs (siRNAs) and microRNAs (miRNAs) have been widely used in mammalian tissue culture and model organisms to selectively silence genes of interest. One limitation of this technology is the lack of precise external control over the gene-silencing event. The use of photocleavable protecting groups installed on nucleobases is a promising strategy to circumvent this limitation, providing high spatial and temporal control over siRNA or miRNA activation. Here, we have designed, synthesized and site-specifically incorporated new photocaged guanosine and uridine RNA phosphoramidites into short RNA duplexes. We demonstrated the applicability of these photocaged siRNAs in the light-regulation of the expression of an exogenous green fluorescent protein reporter gene and an endogenous target gene, the mitosis motor protein, Eg5. Two different approaches were investigated with the caged RNA molecules: the light-regulation of catalytic RNA cleavage by RISC and the light-regulation of seed region recognition. The ability to regulate both functions with light enables the application of this optochemical methodology to a wide range of small regulatory RNA molecules.}, number={22}, journal={NUCLEIC ACIDS RESEARCH}, author={Govan, Jeane M. and Young, Douglas D. and Lusic, Hrvoje and Liu, Qingyang and Lively, Mark O. and Deiters, Alexander}, year={2013}, month={Dec}, pages={10518–10528} }
 @article{prokup_hemphill_deiters_2012, title={DNA Computation: A Photochemically Controlled AND Gate}, volume={134}, ISSN={["0002-7863"]}, DOI={10.1021/ja210050s}, abstractNote={DNA computation is an emerging field that enables the assembly of complex circuits based on defined DNA logic gates. DNA-based logic gates have previously been operated through purely chemical means, controlling logic operations through DNA strands or other biomolecules. Although gates can operate through this manner, it limits temporal and spatial control of DNA-based logic operations. A photochemically controlled AND gate was developed through the incorporation of caged thymidine nucleotides into a DNA-based logic gate. By using light as the logic inputs, both spatial control and temporal control were achieved. In addition, design rules for light-regulated DNA logic gates were derived. A step-response, which can be found in a controller, was demonstrated. Photochemical inputs close the gap between DNA computation and silicon-based electrical circuitry, since light waves can be directly converted into electrical output signals and vice versa. This connection is important for the further development of an interface between DNA logic gates and electronic devices, enabling the connection of biological systems with electrical circuits.}, number={8}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Prokup, Alex and Hemphill, James and Deiters, Alexander}, year={2012}, month={Feb}, pages={3810–3815} }
 @article{lang_davis_torres-kolbus_chou_deiters_chin_2012, title={Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction}, volume={4}, ISSN={["1755-4330"]}, DOI={10.1038/nchem.1250}, abstractNote={The site-specific incorporation of bioorthogonal groups via genetic code expansion provides a powerful general strategy for site-specifically labelling proteins with any probe. However, the slow reactivity of the bioorthogonal functional groups that can be encoded genetically limits the utility of this strategy. We demonstrate the genetic encoding of a norbornene amino acid using the pyrrolysyl tRNA synthetase/tRNACUA pair in Escherichia coli and mammalian cells. We developed a series of tetrazine-based probes that exhibit ‘turn-on’ fluorescence on their rapid reaction with norbornenes. We demonstrate that the labelling of an encoded norbornene is specific with respect to the entire soluble E. coli proteome and thousands of times faster than established encodable bioorthogonal reactions. We show explicitly the advantages of this approach over state-of-the-art bioorthogonal reactions for protein labelling in vitro and on mammalian cells, and demonstrate the rapid bioorthogonal site-specific labelling of a protein on the mammalian cell surface. The site-specific incorporation of a norbornene amino acid into proteins via genetic code expansion, together with the synthesis of a series of tetrazine-based probes that exhibit turn-on fluorescence on their fast cycloaddition with norbornene, enables rapid protein labelling on mammalian cells.}, number={4}, journal={NATURE CHEMISTRY}, author={Lang, Kathrin and Davis, Lloyd and Torres-Kolbus, Jessica and Chou, Chungjung and Deiters, Alexander and Chin, Jason W.}, year={2012}, month={Apr}, pages={298–304} }
 @article{connelly_thomas_deiters_2012, title={High-Throughput Luciferase Reporter Assay for Small-Molecule Inhibitors of MicroRNA Function}, volume={17}, ISSN={["1087-0571"]}, DOI={10.1177/1087057112439606}, abstractNote={MicroRNAs (miRNAs) are endogenous, single-stranded, noncoding RNAs of 21 to 23 nucleotides that regulate gene expression, typically by binding the 3′ untranslated regions of target messenger RNAs. It is estimated that miRNAs are involved in the regulation of 30% of all genes and almost every genetic pathway. Recently, the misregulation of miRNAs has been linked to various human diseases including cancer and viral infections, identifying miRNAs as potential targets for drug discovery. Thus, small-molecule modifiers of miRNAs could serve as lead structures for the development of new therapeutic agents and be useful tools in the elucidation of detailed mechanisms of miRNA function. As a result, we have developed a high-throughput screen for potential small-molecule regulators of the liver-specific microRNA miR-122, which is involved in hepatocellular carcinoma development and hepatitis C virus infection. Our small-molecule screen employs a Huh7 human hepatoma cell line stably transfected with a Renilla luciferase sensor for endogenous miR-122. The assay was optimized and validated using an miR-122 antisense agent and a previously identified small-molecule miR-122 inhibitor. The described reporter assay will enable the high-throughput screening of small-molecule miR-122 inhibitors and can be readily extended to other miRNAs.}, number={6}, journal={JOURNAL OF BIOMOLECULAR SCREENING}, author={Connelly, Colleen M. and Thomas, Meryl and Deiters, Alexander}, year={2012}, month={Jul}, pages={822–828} }
 @article{govan_mciver_riggsbee_deiters_2012, title={Hydrogen Peroxide Induced Activation of Gene Expression in Mammalian Cells using Boronate Estrone Derivatives}, volume={51}, ISSN={["1521-3773"]}, DOI={10.1002/anie.201203222}, abstractNote={Keeping the boron out of the ER: A genetic switch was engineered that activates gene expression in the presence of H(2)O(2). The use of a boronate group on an estrone molecule allows for activation of gene expression through binding of the estrogen receptor only when the boron group is oxidized by H(2)O(2). This sensor is highly sensitive and specific for H(2)O(2).}, number={36}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Govan, Jeane M. and McIver, Andrew L. and Riggsbee, Chad and Deiters, Alexander}, year={2012}, pages={9066–9070} }
 @misc{gardner_deiters_2012, title={Light-controlled synthetic gene circuits}, volume={16}, ISSN={["1367-5931"]}, DOI={10.1016/j.cbpa.2012.04.010}, abstractNote={Highly complex synthetic gene circuits have been engineered in living organisms to develop systems with new biological properties. A precise trigger to activate or deactivate these complex systems is desired in order to tightly control different parts of a synthetic or natural network. Light represents an excellent tool to achieve this goal as it can be regulated in timing, location, intensity, and wavelength, which allows for precise spatiotemporal control over genetic circuits. Recently, light has been used as a trigger to control the biological function of small molecules, oligonucleotides, and proteins involved as parts in gene circuits. Light activation has enabled the construction of unique systems in living organisms such as band-pass filters and edge-detectors in bacterial cells. Additionally, light also allows for the regulation of intermediate steps of complex dynamic pathways in mammalian cells such as those involved in kinase networks. Herein we describe recent advancements in the area of light-controlled synthetic networks.}, number={3-4}, journal={CURRENT OPINION IN CHEMICAL BIOLOGY}, author={Gardner, Laura and Deiters, Alexander}, year={2012}, month={Aug}, pages={292–299} }
 @article{arbely_torres-kolbus_deiters_chin_2012, title={Photocontrol of Tyrosine Phosphorylation in Mammalian Cells via Genetic Encoding of Photocaged Tyrosine}, volume={134}, ISSN={["0002-7863"]}, DOI={10.1021/ja3046958}, abstractNote={We report the first site-specific genetic encoding of photocaged tyrosine into proteins in mammalian cells. By photocaging Tyr701 of STAT1 we demonstrate that it is possible to photocontrol tyrosine phosphorylation and signal transduction in mammalian cells.}, number={29}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Arbely, Eyal and Torres-Kolbus, Jessica and Deiters, Alexander and Chin, Jason W.}, year={2012}, month={Jul}, pages={11912–11915} }
 @article{govan_uprety_hemphill_lively_deiters_2012, title={Regulation of transcription through light-activation and light-deactivation of triplex-forming oligonucleotides in mammalian cells}, volume={7}, DOI={10.1021/cb300161r}, abstractNote={Triplex-forming oligonucleotides (TFOs) are efficient tools to regulate gene expression through the inhibition of transcription. Here, nucleobase-caging technology was applied to the temporal regulation of transcription through light-activated TFOs. Through site-specific incorporation of caged thymidine nucleotides, the TFO:DNA triplex formation is blocked, rendering the TFO inactive. However, after a brief UV irradiation, the caging groups are removed, activating the TFO and leading to the inhibition of transcription. Furthermore, the synthesis and site-specific incorporation of caged deoxycytidine nucleotides within TFO inhibitor sequences was developed, allowing for the light-deactivation of TFO function and thus photochemical activation of gene expression. After UV-induced removal of the caging groups, the TFO forms a DNA dumbbell structure, rendering it inactive, releasing it from the DNA, and activating transcription. These are the first examples of light-regulated TFOs and their application in the photochemical activation and deactivation of gene expression. In addition, hairpin loop structures were found to significantly increase the efficacy of phosphodiester DNA-based TFOs in tissue culture.}, number={7}, journal={ACS Chemical Biology}, author={Govan, J. M. and Uprety, R. and Hemphill, J. and Lively, M. O. and Deiters, A.}, year={2012}, pages={1247–1256} }
 @article{connelly_uprety_hemphill_deiters_2012, title={Spatiotemporal control of microRNA function using light-activated antagomirs}, volume={8}, ISSN={["1742-206X"]}, DOI={10.1039/c2mb25175b}, abstractNote={MicroRNAs (miRNAs) are small non-coding RNAs that act as post-transcriptional gene regulators and have been shown to regulate many biological processes including embryonal development, cell differentiation, apoptosis, and proliferation. Variations in the expression of certain miRNAs have been linked to a wide range of human diseases - especially cancer - and the diversity of miRNA targets suggests that they are involved in various cellular networks. Several tools have been developed to control the function of individual miRNAs and have been applied to study their biogenesis, biological role, and therapeutic potential; however, common methods lack a precise level of control that allows for the study of miRNA function with high spatial and temporal resolution. Light-activated miRNA antagomirs for mature miR-122 and miR-21 were developed through the site-specific installation of caging groups on the bases of selected nucleotides. Installation of caged nucleotides led to complete inhibition of the antagomir-miRNA hybridization and thus inactivation of antagomir function. The miRNA-inhibitory activity of the caged antagomirs was fully restored upon decaging through a brief UV irradiation. The synthesized antagomirs were applied to the photochemical regulation of miRNA function in mammalian cells. Moreover, spatial control over antagomir activity was obtained in mammalian cells through localized UV exposure. The presented approach enables the precise regulation of miRNA function and miRNA networks with unprecedented spatial and temporal resolution using UV irradiation and can be extended to any miRNA of interest.}, number={11}, journal={MOLECULAR BIOSYSTEMS}, author={Connelly, Colleen M. and Uprety, Rajendra and Hemphill, James and Deiters, Alexander}, year={2012}, pages={2987–2993} }
 @article{morckel_lusic_farzana_yoder_deiters_nascone-yoder_2011, title={A photoactivatable small-molecule inhibitor for light-controlled spatiotemporal regulation of Rho kinase in live embryos}, volume={139}, ISSN={0950-1991 1477-9129}, url={http://dx.doi.org/10.1242/dev.072165}, DOI={10.1242/dev.072165}, abstractNote={To uncover the molecular mechanisms of embryonic development, the ideal loss-of-function strategy would be capable of targeting specific regions of the living embryo with both temporal and spatial precision. To this end, we have developed a novel pharmacological agent that can be light activated to achieve spatiotemporally limited inhibition of Rho kinase activity in vivo. A new photolabile caging group, 6-nitropiperonyloxymethyl (NPOM), was installed on a small-molecule inhibitor of Rho kinase, Rockout, to generate a ‘caged Rockout’ derivative. Complementary biochemical, cellular, molecular and morphogenetic assays in both mammalian cell culture and Xenopus laevis embryos validate that the inhibitory activity of the caged compound is dependent on exposure to light. Conveniently, this unique reagent retains many of the practical advantages of conventional small-molecule inhibitors, including delivery by simple diffusion in the growth medium and concentration-dependent tuneability, but can be locally activated by decaging with standard instrumentation. Application of this novel tool to the spatially heterogeneous problem of embryonic left-right asymmetry revealed a differential requirement for Rho signaling on the left and right sides of the primitive gut tube, yielding new insight into the molecular mechanisms that generate asymmetric organ morphology. As many aromatic/heterocyclic small-molecule inhibitors are amenable to installation of this caging group, our results indicate that photocaging pharmacological inhibitors might be a generalizable technique for engendering convenient loss-of-function reagents with great potential for wide application in developmental biology.}, number={2}, journal={Development}, publisher={The Company of Biologists}, author={Morckel, A. R. and Lusic, H. and Farzana, L. and Yoder, J. A. and Deiters, A. and Nascone-Yoder, N. M.}, year={2011}, month={Dec}, pages={437–442} }
 @article{zou_lin_maggard_deiters_2011, title={Efficacy of C-N Coupling Reactions with a New Multinuclear Copper Complex Catalyst and Its Dissociation into Mononuclear Species}, volume={2011}, ISSN={["1099-0690"]}, DOI={10.1002/ejoc.201100399}, abstractNote={Abstract}, number={22}, journal={EUROPEAN JOURNAL OF ORGANIC CHEMISTRY}, author={Zou, Yan and Lin, Haisheng and Maggard, Paul A. and Deiters, Alexander}, year={2011}, month={Aug}, pages={4154–4159} }
 @article{chou_uprety_davis_chin_deiters_2011, title={Genetically encoding an aliphatic diazirine for protein photocrosslinking}, volume={2}, ISSN={["2041-6539"]}, DOI={10.1039/c0sc00373e}, abstractNote={Photocrosslinking is an important approach that allows discovery and detailed investigation of protein–protein, protein–oligonucleotide, and protein–small molecule interactions with high temporal and spatial resolution. A major limitation to the universal application of this methodology is the site-specific introduction of efficient aliphatic photocrosslinking probes into proteins of interest. Here, we report a novel aliphatic diazirine amino acid and its genetically encoded, site-specific incorporation into proteins in bacterial and mammalian cells. Furthermore, we demonstrate efficient photocrosslinking of a test proteinin vitro and in vivo.}, number={3}, journal={CHEMICAL SCIENCE}, author={Chou, Chungjung and Uprety, Rajendra and Davis, Lloyd and Chin, Jason W. and Deiters, Alexander}, year={2011}, pages={480–483} }
 @article{dush_mciver_parr_young_fisher_newman_sannes_hauck_deiters_nascone-yoder_2011, title={Heterotaxin: A TGF-beta Signaling Inhibitor Identified in a Multi-Phenotype Profiling Screen in Xenopus Embryos}, volume={18}, ISSN={["1879-1301"]}, DOI={10.1016/j.chembiol.2010.12.008}, abstractNote={Disruptions of anatomical left-right asymmetry result in life-threatening heterotaxic birth defects in vital organs. We performed a small molecule screen for left-right asymmetry phenotypes in Xenopus embryos and discovered a pyridine analog, heterotaxin, which disrupts both cardiovascular and digestive organ laterality and inhibits TGF-β-dependent left-right asymmetric gene expression. Heterotaxin analogs also perturb vascular development, melanogenesis, cell migration, and adhesion, and indirectly inhibit the phosphorylation of an intracellular mediator of TGF-β signaling. This combined phenotypic profile identifies these compounds as a class of TGF-β signaling inhibitors. Notably, heterotaxin analogs also possess highly desirable antitumor properties, inhibiting epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation in mammalian systems. Our results suggest that assessing multiple organ, tissue, cellular, and molecular parameters in a whole organism context is a valuable strategy for identifying the mechanism of action of bioactive compounds.}, number={2}, journal={CHEMISTRY & BIOLOGY}, author={Dush, Michael K. and McIver, Andrew L. and Parr, Meredith A. and Young, Douglas D. and Fisher, Julie and Newman, Donna R. and Sannes, Philip L. and Hauck, Marlene L. and Deiters, Alexander and Nascone-Yoder, Nanette}, year={2011}, month={Feb}, pages={252–263} }
 @article{karginov_zou_shirvanyants_kota_dokholyan_young_hahn_deiters_2011, title={Light Regulation of Protein Dimerization and Kinase Activity in Living Cells Using Photocaged Rapamycin and Engineered FKBP}, volume={133}, ISSN={["0002-7863"]}, DOI={10.1021/ja109630v}, abstractNote={We developed a new system for light-induced protein dimerization in living cells using a photocaged analogue of rapamycin together with an engineered rapamycin binding domain. Using focal adhesion kinase as a target, we demonstrated successful light-mediated regulation of protein interaction and localization in living cells. Modification of this approach enabled light-triggered activation of a protein kinase and initiation of kinase-induced phenotypic changes in vivo.}, number={3}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Karginov, Andrei V. and Zou, Yan and Shirvanyants, David and Kota, Pradeep and Dokholyan, Nikolay V. and Young, Douglas D. and Hahn, Klaus M. and Deiters, Alexander}, year={2011}, month={Jan}, pages={420–423} }
 @article{chou_deiters_2011, title={Light-Activated Gene Editing with a Photocaged Zinc-Finger Nuclease}, volume={50}, ISSN={["1433-7851"]}, DOI={10.1002/anie.201101157}, abstractNote={A general approach for targeted gene modification with precise external control and high spatial and temporal resolution will greatly advance investigations in genetics, gene therapy, and developmental biology. However, traditional methods such as homologous recombination[1] and nonhomologous end joining[2] for the introduction and deletion of genomic DNA sequences usually display very low efficiency in vivo, thus limiting their applicability. Recently, the efficiency of these processes has been greatly improved by the ability to site-specifically introduce doublestrand breaks (DSBs) into genomic DNA.[3,4] A family of artificial restriction enzymes, namely zinc-finger nucleases (ZFN), has been developed to sequence-selectively achieve dsDNA scission. ZFNs have since emerged as important and widely recognized tools for the genetic modification of cells, model organisms, and possibly humans to investigate gene function and to treat genetic disorders.[5–9]}, number={30}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Chou, Chungjung and Deiters, Alexander}, year={2011}, pages={6839–6842} }
 @article{gautier_deiters_chin_2011, title={Light-Activated Kinases Enable Temporal Dissection of Signaling Networks in Living Cells}, volume={133}, ISSN={["1520-5126"]}, DOI={10.1021/ja1109979}, abstractNote={We report a general strategy for creating protein kinases in mammalian cells that are poised for very rapid activation by light. By photoactivating a caged version of MEK1, we demonstrate the specific, rapid, and receptor independent activation of an artificial subnetwork within the Raf/MEK/ERK pathway. Time-lapse microscopy allowed us to precisely characterize the kinetics of elementary steps in the signaling cascade and provided insight into adaptive feedback and rate-determining processes in the pathway.}, number={7}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Gautier, Arnaud and Deiters, Alexander and Chin, Jason W.}, year={2011}, month={Feb}, pages={2124–2127} }
 @article{govan_lively_deiters_2011, title={Photochemical Control of DNA Decoy Function Enables Precise Regulation of Nuclear Factor kappa B Activity}, volume={133}, ISSN={["0002-7863"]}, DOI={10.1021/ja204980v}, abstractNote={DNA decoys have been developed for the inhibition of transcriptional regulation of gene expression. However, the present methodology lacks the spatial and temporal control of gene expression that is commonly found in nature. Here, we report the application of photoremovable protecting groups on nucleobases of nuclear factor κB (NF-κB) DNA decoys to regulate NF-κB-driven transcription of secreted alkaline phosphatase using light as an external control element. The NF-κB family of proteins is comprised of important eukaryotic transcription factors that regulate a wide range of cellular processes and are involved in immune response, development, cellular growth, and cell death. Several diseases, including cancer, arthritis, chronic inflammation, asthma, neurodegenerative diseases, and heart disease, have been linked to constitutively active NF-κB. Through the direct incorporation of caging groups into an NF-κB decoy, we were able to disrupt DNA:DNA hybridization and inhibit the binding of the transcription factor to the DNA decoy until UV irradiation removed the caging groups and restored the activity of the oligonucleotide. Excellent light-switching behavior of transcriptional regulation was observed. This is the first example of a caged DNA decoy for the photochemical regulation of gene expression in mammalian cells and represents an important addition to the toolbox of light-controlled gene regulatory agents.}, number={33}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Govan, Jeane M. and Lively, Mark O. and Deiters, Alexander}, year={2011}, month={Aug}, pages={13176–13182} }
 @article{gardner_zou_mara_cropp_deiters_2011, title={Photochemical control of bacterial signal processing using a light-activated erythromycin}, volume={7}, ISSN={["1742-206X"]}, DOI={10.1039/c1mb05166k}, abstractNote={Bacterial cells control resistance to the macrolide antibiotic erythromycin using the MphR(A) repressor protein. Erythromycin binds to MphR(A), causing release of the PmphR promoter, activating expression of the 2'-phosphotransferase Mph(A). We engineered the MphR(A)/promoter system to, in conjunction with a light-activatable derivative of erythromycin, enable photochemical activation of gene expression in E. coli. We applied this photochemical gene switch to the construction of a light-triggered logic gate, a light-controlled band-pass filter, as well as spatial and temporal control of gene expression.}, number={9}, journal={MOLECULAR BIOSYSTEMS}, author={Gardner, Laura and Zou, Yan and Mara, Alexandria and Cropp, T. Ashton and Deiters, Alexander}, year={2011}, pages={2554–2557} }
 @article{govan_mciver_deiters_2011, title={Stabilization and Photochemical Regulation of Antisense Agents through PEGylation}, volume={22}, ISSN={["1520-4812"]}, DOI={10.1021/bc200411n}, abstractNote={Oligonucleotides are effective tools for the regulation of gene expression in cell culture and model organisms, most importantly through antisense mechanisms. Due to the inherent instability of DNA antisense agents, various modifications have been introduced to increase the efficacy of oligonucleotides, including phosphorothioate DNA, locked nucleic acids, peptide nucleic acids, and others. Here, we present antisense agent stabilization through conjugation of a poly(ethylene glycol) (PEG) group to a DNA oligonucleotide. By employing a photocleavable linker between the PEG group and the antisense agent, we were able to achieve light-induced deactivation of antisense activity. The bioconjugated PEG group provides stability to the DNA antisense agent without affecting its native function of silencing gene expression via RNase H-catalyzed mRNA degradation. Once irradiated with UV light of 365 nm, the PEG group is cleaved from the antisense agent leaving the DNA unprotected and open for degradation by endogenous nucleases, thereby restoring gene expression. By using a photocleavable PEG group (PhotoPEG), antisense activity can be regulated with high spatial and temporal resolution, paving the way for precise regulation of gene expression in biological systems.}, number={10}, journal={BIOCONJUGATE CHEMISTRY}, author={Govan, Jeane M. and McIver, Andrew L. and Deiters, Alexander}, year={2011}, month={Oct}, pages={2136–2142} }
 @article{zou_liu_deiters_2011, title={Synthesis of the Pyridine Core of Cyclothiazomycin}, volume={13}, ISSN={["1523-7052"]}, DOI={10.1021/ol201682k}, abstractNote={A highly convergent synthesis of the pyridine core of the thiopeptide antibiotic cyclothiazomycin has been developed based on a [2+2+2] cyclotrimerization key step. The regioselective assembly of the heterocyclic center of this important class of antibiotics takes advantage of a temporary silicon tether and the ruthenium-catalyzed cyclotrimerization reaction of a diyne and an electron-poor thiazole nitrile.}, number={16}, journal={ORGANIC LETTERS}, author={Zou, Yan and Liu, Qingyang and Deiters, Alexander}, year={2011}, month={Aug}, pages={4352–4355} }
 @article{bilbille_gustilo_harris_jones_lusic_kaiser_delano_spremulli_deiters_agris_2011, title={The Human Mitochondrial tRNA(Met): Structure/Function Relationship of a Unique Modification in the Decoding of Unconventional Codons}, volume={406}, ISSN={["1089-8638"]}, DOI={10.1016/j.jmb.2010.11.042}, abstractNote={Human mitochondrial mRNAs utilize the universal AUG and the unconventional isoleucine AUA codons for methionine. In contrast to translation in the cytoplasm, human mitochondria use one tRNA, hmtRNA(Met)(CAU), to read AUG and AUA codons at both the peptidyl- (P-), and aminoacyl- (A-) sites of the ribosome. The hmtRNA(Met)(CAU) has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position 34 (f(5)C(34)), and a cytidine substituting for the invariant uridine at position 33 of the canonical U-turn in tRNAs. The structure of the tRNA anticodon stem and loop domain (hmtASL(Met)(CAU)), determined by NMR restrained molecular modeling, revealed how the f(5)C(34) modification facilitates the decoding of AUA at the P- and the A-sites. The f(5)C(34) defined a reduced conformational space for the nucleoside, in what appears to have restricted the conformational dynamics of the anticodon bases of the modified hmtASL(Met)(CAU). The hmtASL(Met)(CAU) exhibited a C-turn conformation that has some characteristics of the U-turn motif. Codon binding studies with both Escherichia coli and bovine mitochondrial ribosomes revealed that the f(5)C(34) facilitates AUA binding in the A-site and suggested that the modification favorably alters the ASL binding kinetics. Mitochondrial translation by many organisms, including humans, sometimes initiates with the universal isoleucine codons AUU and AUC. The f(5)C(34) enabled P-site codon binding to these normally isoleucine codons. Thus, the physicochemical properties of this one modification, f(5)C(34), expand codon recognition from the traditional AUG to the non-traditional, synonymous codons AUU and AUC as well as AUA, in the reassignment of universal codons in the mitochondria.}, number={2}, journal={JOURNAL OF MOLECULAR BIOLOGY}, author={Bilbille, Yann and Gustilo, Estella M. and Harris, Kimberly A. and Jones, Christie N. and Lusic, Hrvoje and Kaiser, Robert J. and Delano, Michael O. and Spremulli, Linda L. and Deiters, Alexander and Agris, Paul F.}, year={2011}, month={Feb}, pages={257–274} }
 @article{young_lively_deiters_2010, title={Activation and Deactivation of DNAzyme and Antisense Function with Light for the Photochemical Regulation of Gene Expression in Mammalian Cells}, volume={132}, ISSN={["1520-5126"]}, DOI={10.1021/ja100710j}, abstractNote={The photochemical regulation of biological systems represents a very precise means of achieving high-resolution control over gene expression in both a spatial and a temporal fashion. DNAzymes are enzymatically active deoxyoligonucleotides that enable the site-specific cleavage of RNA and have been used in a variety of in vitro applications. We have previously reported the photochemical activation of DNAzymes and antisense agents through the preparation of a caged DNA phosphoramidite and its site-specific incorporation into oligonucleotides. The presence of the caging group disrupts either DNA:RNA hybridization or catalytic activity until removed via a brief irradiation with UV light. Here, we are expanding this concept by investigating the photochemical deactivation of DNAzymes and antisense agents. Moreover, we report the application of light-activated and light-deactivated antisense agents to the regulation of gene function in mammalian cells. This represents the first example of gene silencing antisense agents that can be turned on and turned off in mammalian tissue culture.}, number={17}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Young, Douglas D. and Lively, Mark O. and Deiters, Alexander}, year={2010}, month={May}, pages={6183–6193} }
 @article{hancock_uprety_deiters_chin_2010, title={Expanding the Genetic Code of Yeast for Incorporation of Diverse Unnatural Amino Acids via a Pyrrolysyl-tRNA Synthetase/tRNA Pair}, volume={132}, ISSN={["0002-7863"]}, DOI={10.1021/ja104609m}, abstractNote={We report the discovery of a simple system through which variant pyrrolysyl-tRNA synthetase/tRNACUAPyl pairs created in Escherichia coli can be used to expand the genetic code of Saccharomyces cerevisiae. In the process we have solved the key challenges of producing a functional tRNACUAPyl in yeast and discovered a pyrrolysyl-tRNA synthetase/tRNACUAPyl pair that is orthogonal in yeast. Using our approach we have incorporated an alkyne-containing amino acid for click chemistry, an important post-translationally modified amino acid and one of its analogs, a photocaged amino acid and a photo-cross-linking amino acid into proteins in yeast. Extensions of our approach will allow the growing list of useful amino acids that have been incorporated in E. coli with variant pyrrolysyl-tRNA synthetase/tRNACUAPyl pairs to be site-specifically incorporated into proteins in yeast.}, number={42}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Hancock, Susan M. and Uprety, Rajendra and Deiters, Alexander and Chin, Jason W.}, year={2010}, month={Oct}, pages={14819–14824} }
 @article{miyake-stoner_refakis_hammill_lusic_hazen_deiters_mehl_2010, title={Generating Permissive Site-Specific Unnatural Aminoacyl-tRNA Synthetases}, volume={49}, ISSN={["0006-2960"]}, DOI={10.1021/bi901947r}, abstractNote={Genetically incorporated unnatural amino acid (UAA) technologies are powerful tools that are greatly enhancing our ability to study and engineer biological systems. Using these techniques, researchers can precisely control the position and number of novel chemical moieties in a protein, via introducing the novel R group of UAAs, that are genetically encoded in the protein's primary structure. The substrate recognition properties of a natural aminoacyl-tRNA synthetase (aaRS) must be modified in order to incorporate UAAs into proteins. Protocols to do so are technically simple but require time and optimization, which has significantly limited the accessibility of this important technology. At present, engineered unnatural aminoacyl-tRNA synthetases (UaaRS) are evaluated on their translational efficiency (the extent to which they allow for incorporation of UAAs into protein) and fidelity (the extent to which they prevent incorporation of natural amino acids). We propose that a third parameter of substrate recognition, permissivity, is equally important. Permissive UaaRSs, whose relaxed substrate recognition properties allow them to incorporate multiple unnatural amino acids (but not natural amino acids), would eliminate the need to generate new UaaRSs for many new UAAs. Here, we outline methods for quickly and easily assessing the permissivity of existing UaaRSs and for generating permissive UaaRSs. In proof of principle experiments, we determined the degree of permissivity of two UaaRSs for a family of structurally related fluorinated UAAs ((19)F-UAAs). We then increased the permissivity of the initial UaaRSs to allow for incorporation of the family of (19)F-UAAs. Finally, we validated the utility of these new (19)F-UAAs as probes for fluorine NMR studies of protein structure and dynamics. We expect that results of this work will increase the accessibility of UAA technology and the use of new UAAs in proteins.}, number={8}, journal={BIOCHEMISTRY}, author={Miyake-Stoner, Shigeki J. and Refakis, Christian A. and Hammill, Jared T. and Lusic, Hrvoje and Hazen, Jennifer L. and Deiters, Alexander and Mehl, Ryan A.}, year={2010}, month={Mar}, pages={1667–1677} }
 @article{gautier_nguyen_lusic_an_deiters_chin_2010, title={Genetically encoded photocontrol of protein localization in mammalian cells}, volume={132}, number={12}, journal={Journal of the American Chemical Society}, author={Gautier, A. and Nguyen, D. P. and Lusic, H. and An, W. A. and Deiters, A. and Chin, J. W.}, year={2010}, pages={4086-} }
 @article{lusic_uprety_deiters_2010, title={Improved Synthesis of the Two-Photon Caging Group 3-Nitro-2-Ethyldibenzofuran and Its Application to a Caged Thymidine Phosphoramidite}, volume={12}, ISSN={["1523-7060"]}, DOI={10.1021/ol902807q}, abstractNote={A new and efficient route to the recently reported 3-nitro-2-ethyldibenzofuran caging group was developed. Furthermore, its installation on a thymidine phosphoramidite is described. This caging group is efficiently removed through light-irradiation at 365 nm.}, number={5}, journal={ORGANIC LETTERS}, author={Lusic, Hrvoje and Uprety, Rajendra and Deiters, Alexander}, year={2010}, month={Mar}, pages={916–919} }
 @article{deiters_garner_lusic_govan_dush_nascone-yoder_yoder_2010, title={Photocaged Morpholino Oligomers for the Light-Regulation of Gene Function in Zebrafish and Xenopus Embryos}, volume={132}, ISSN={0002-7863 1520-5126}, url={http://dx.doi.org/10.1021/ja1053863}, DOI={10.1021/ja1053863}, abstractNote={Morpholino oligonucleotides, or morpholinos, have emerged as powerful antisense reagents for evaluating gene function in both in vitro and in vivo contexts. However, the constitutive activity of these reagents limits their utility for applications that require spatiotemporal control, such as tissue-specific gene disruptions in embryos. Here we report a novel and efficient synthetic route for incorporating photocaged monomeric building blocks directly into morpholino oligomers and demonstrate the utility of these caged morpholinos in the light-activated control of gene function in both cell culture and living embryos. We demonstrate that a caged morpholino that targets enhanced green fluorescent protein (EGFP) disrupts EGFP production only after exposure to UV light in both transfected cells and living zebrafish (Danio rerio) and Xenopus frog embryos. Finally, we show that a caged morpholino targeting chordin, a zebrafish gene that yields a distinct phenotype when functionally disrupted by conventional morpholinos, elicits a chordin phenotype in a UV-dependent manner. Our results suggest that photocaged morpholinos are readily synthesized and highly efficacious tools for light-activated spatiotemporal control of gene expression in multiple contexts.}, number={44}, journal={Journal of the American Chemical Society}, publisher={American Chemical Society (ACS)}, author={Deiters, Alexander and Garner, R. Aaron and Lusic, Hrvoje and Govan, Jeane M. and Dush, Mike and Nascone-Yoder, Nanette M. and Yoder, Jeffrey A.}, year={2010}, month={Nov}, pages={15644–15650} }
 @article{chou_young_deiters_2010, title={Photocaged T7 RNA Polymerase for the Light Activation of Transcription and Gene Function in Pro- and Eukaryotic Cells}, volume={11}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.201000041}, abstractNote={Abstract}, number={7}, journal={CHEMBIOCHEM}, author={Chou, Chungjung and Young, Douglas D. and Deiters, Alexander}, year={2010}, month={May}, pages={972–977} }
 @article{georgianna_lusic_mclver_deiters_2010, title={Photocleavable Polyethylene Glycol for the Light-Regulation of Protein Function}, volume={21}, ISSN={["1043-1802"]}, DOI={10.1021/bc100084n}, abstractNote={PEGylation is commonly employed to enhance the pharmacokinetic properties of proteins, but it can interfere with natural protein function. Protein activity can thus be abrogated through PEGylation, and a controllable means to remove the polyethylene glycol (PEG) group from the protein is desirable. As such, light affords a unique control over biomolecules through the application of photosensitive groups. Herein, we report the synthesis of a photocleavable PEG reagent (PhotoPEG) and its application to the light-regulation of enzyme activity.}, number={8}, journal={BIOCONJUGATE CHEMISTRY}, author={Georgianna, Wesleigh E. and Lusic, Hrvoje and Mclver, Andrew L. and Deiters, Alexander}, year={2010}, month={Aug}, pages={1404–1407} }
 @article{deiters_2010, title={Principles and Applications of the Photochemical Control of Cellular Processes}, volume={11}, ISSN={["1439-4227"]}, DOI={10.1002/cbic.200900529}, abstractNote={Biological processes, particularly gene function, are naturally regulated with high spatiotemporal resolution in single cells and multicellular organisms. The activity of genes, proteins, and other biological molecules is precisely controlled in timing and location. This is especially evident during the complex biological processes observed in the development of an organism. In order to understand and to study these processes and their misregulation in human disease, it is imperative to control them with the same level of spatiotemporal resolution found in nature. Here, light irradiation represents a unique tool, because it can be easily and precisely controlled in timing, location, and amplitude; thus, light enables the precise activation and deactivation of biological function. 
 
Rather than providing a comprehensive literature review, this article focuses on the basic concepts and requirements of controlling biological (especially cellular) function with light. Recent examples are used to illustrate these concepts. The interested reader can find additional excellent and comprehensive reviews regarding the photochemical regulation of biologically active molecules in the literature.[1]}, number={1}, journal={CHEMBIOCHEM}, author={Deiters, Alexander}, year={2010}, month={Jan}, pages={47–53} }
 @misc{riggsbee_deiters_2010, title={Recent advances in the photochemical control of protein function}, volume={28}, ISSN={["1879-3096"]}, DOI={10.1016/j.tibtech.2010.06.001}, abstractNote={Biological processes are regulated with a high level of spatial and temporal resolution. To understand and manipulate these processes, scientists need to be able to regulate them with Nature's level of precision. In this context, light is a unique regulatory element because it can be precisely controlled in terms of location, timing and amplitude. Moreover, most biological laboratories have a wide range of light sources as standard equipment. This review article summarizes the most recent advances in light-mediated regulation of protein function and its application in a cellular context. Specifically, the photocaging of small-molecule modulators of protein function and of specific amino acid residues in proteins is discussed. In addition, examples of the photochemical control of protein function through the application of genetically engineered natural-light receptors are presented.}, number={9}, journal={TRENDS IN BIOTECHNOLOGY}, author={Riggsbee, Chad W. and Deiters, Alexander}, year={2010}, month={Sep}, pages={468–475} }
 @article{georgianna_deiters_2010, title={Reversible light switching of cell signalling by genetically encoded protein dimerization}, volume={11}, DOI={10.1002/cbic.200900754}, abstractNote={Regulation of intracellular processes, for example, nucleic acid, protein, and small-molecule function, occurs with a high level of precision and timing. In order to understand and control these processes, tools are required that mimic the degree of spatiotemporal control found in nature. As such, light affords a noninvasive tool for tightly controlling biological function; it can be easily modified in amplitude, location, and duration to afford spatial and temporal control over a cellular event of interest. Photochemical control has traditionally been achieved through the installation of a photolabile protecting group, termed caging group, onto a biomolecule of interest. The caged molecule is thus rendered temporarily inactive, either through steric blocking of molecular interactions or by preventing chemical reactions performed by the caged functional group. Upon irradiation with UV light, the caging group is removed, and nascent biological activity is restored. Classic photocaging groups are based on an ortho-nitrobenzyl core requiring UV irradiation, although newer caging groups based on the two-photon decaging of quinoline, dibenzofuran and coumarin moieties through IR irradiation have also been developed. While caging groups provide an effective means to control biological processes with light, limitations include the irreversibility of the decaging reaction and difficulties in the genetic encoding of caged molecules. While photocaging is appropriate for many applications, a means to achieve light-activated spatiotemporal control of a genetically encoded process in a reversible fashion would be ideal. Recently, genetically encoded photoresponsive systems have been described that utilize naturally occurring light-sensitive biomolecules, such as those found in phototropic plants. For example, fusion to the light oxygen voltage (LOV) domain of phototropin has been used to reversibly inhibit protein activity. In the absence of light, the effector binding site of the LOV-fused protein is sterically blocked by the LOV domain-Ja motif. Irradiation at 458 nm induces a conformation change in the Ja helix that frees the active site of the protein, thereby restoring its activity. This technology enables the application of light toward the genetically encoded, reversible photoregulation of a cellular event. Previously, a light-switchable transcriptional activator was constructed from a protein–protein interaction module in the phytochrome signalling network of the plant Arabidopsis thaliana. Phytochrome proteins (e.g. , PhyB) regulate many lightresponsive pathways in Arabidopsis. Upon exposure to red light at 650 nm, the phycocyanobilin chromophore (PCB, Scheme 1), covalently bound to PhyB, undergoes a light-induced Z/E photoisomerization at a single double bond, which}, number={3}, journal={Chembiochem}, author={Georgianna, W. E. and Deiters, A.}, year={2010}, pages={301–303} }
 @article{wilkins_marionni_young_liu_wang_di salvo_deiters_cropp_2010, title={Site-Specific Incorporation of Fluorotyrosines into Proteins in Escherichia coli by Photochemical Disguise}, volume={49}, ISSN={["0006-2960"]}, DOI={10.1021/bi100013s}, abstractNote={Fluorinated analogues of tyrosine can be used to manipulate the electronic environments of protein active sites. The ability to selectively mutate tyrosine residues to fluorotyrosines is limited, however, and can currently only be achieved through the total synthesis of proteins. As a general solution to this problem, we genetically encoded the unnatural amino acids o-nitrobenzyl-2-fluorotyrosine, -3-fluorotyrosine, and -2,6-difluorotyrosine in Escherichia coli. These amino acids are disguised from recognition by the endogenous protein biosynthetic machinery, effectively preventing global incorporation of fluorotyrosine into proteins.}, number={8}, journal={BIOCHEMISTRY}, author={Wilkins, Bryan J. and Marionni, Samuel and Young, Douglas D. and Liu, Jia and Wang, Yan and Di Salvo, Martino L. and Deiters, Alexander and Cropp, T. Ashton}, year={2010}, month={Mar}, pages={1557–1559} }
 @article{young_connelly_grohmann_deiters_2010, title={Small Molecule Modifiers of MicroRNA miR-122 Function for the Treatment of Hepatitis C Virus Infection and Hepatocellular Carcinoma}, volume={132}, ISSN={["1520-5126"]}, DOI={10.1021/ja910275u}, abstractNote={MicroRNAs are a recently discovered new class of important endogenous regulators of gene function. Aberrant regulation of microRNAs has been linked to various human diseases, most importantly cancer. Small molecule intervention of microRNA misregulation has the potential to provide new therapeutic approaches to such diseases. Here, we report the first small molecule inhibitors and activators of the liver-specific microRNA miR-122. This microRNA is the most abundant microRNA in the liver and is involved in hepatocellular carcinoma development and hepatitis C virus (HCV) infection. Our small molecule inhibitors reduce viral replication in liver cells and represent a new approach to the treatment of HCV infections. Moreover, small molecule activation of miR-122 in liver cancer cells selectively induced apoptosis through caspase activation, thus having implications in cancer chemotherapy. In addition to providing a new approach for the development of therapeutics, small molecule modifiers of miR-122 function are unique tools for exploring miR-122 biogenesis.}, number={23}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Young, Douglas D. and Connelly, Colleen M. and Grohmann, Christoph and Deiters, Alexander}, year={2010}, month={Jun}, pages={7976–7981} }
 @misc{deiters_2010, title={Small Molecule Modifiers of the microRNA and RNA Interference Pathway}, volume={12}, ISSN={["1550-7416"]}, DOI={10.1208/s12248-009-9159-3}, abstractNote={Recently, the RNA interference (RNAi) pathway has become the target of small molecule inhibitors and activators. RNAi has been well established as a research tool in the sequence-specific silencing of genes in eukaryotic cells and organisms by using exogenous, small, double-stranded RNA molecules of approximately 20 nucleotides. Moreover, a recently discovered post-transcriptional gene regulatory mechanism employs microRNAs (miRNAs), a class of endogenously expressed small RNA molecules, which are processed via the RNAi pathway. The chemical modulation of RNAi has important therapeutic relevance, because a wide range of miRNAs has been linked to a variety of human diseases, especially cancer. Thus, the activation of tumor-suppressive miRNAs and the inhibition of oncogenic miRNAs by small molecules have the potential to provide a fundamentally new approach for the development of cancer therapeutics.}, number={1}, journal={AAPS JOURNAL}, author={Deiters, Alexander}, year={2010}, month={Mar}, pages={51–60} }
 @article{zou_deiters_2010, title={Total Synthesis of Cryptoacetalide}, volume={75}, ISSN={["1520-6904"]}, DOI={10.1021/jo100867v}, abstractNote={We are reporting the first total synthesis of the tetracyclic terpene natural product cryptoacetalide. Key steps of the synthesis are a microwave-mediated [2+2+2] cyclo-trimerization reaction to construct the central benzene ring, and a light-mediated radical cyclization to assemble the spiro-ketal moiety.}, number={15}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Zou, Yan and Deiters, Alexander}, year={2010}, month={Aug}, pages={5355–5358} }
 @article{mciver_deiters_2010, title={Tricyclic Alkaloid Core Structures Assembled by a Cyclotrimerization-Coupled Intramolecular Nucleophilic Substitution Reaction}, volume={12}, ISSN={["1523-7052"]}, DOI={10.1021/ol100177u}, abstractNote={A facile approach to tricyclic alkaloid core structures was developed by sequencing a pyridine-forming [2 + 2 + 2] cyclotrimerization reaction with an intramolecular nucleophilic substitution. This methodology enabled the facile assembly of the spiroindolinone framework of citrinadins A and B, and cyclopiamine B.}, number={6}, journal={ORGANIC LETTERS}, author={McIver, Andrew L. and Deiters, Alexander}, year={2010}, month={Mar}, pages={1288–1291} }
 @article{chou_young_deiters_2009, title={A Light-Activated DNA Polymerase}, volume={48}, ISSN={["1521-3773"]}, DOI={10.1002/anie.200901115}, abstractNote={When the time is right: The widely applied Thermus aquaticus DNA polymerase was rendered light-activatable by incorporation of the photocaged amino acid ortho-nitrobenzyl tyrosine in place of a key tyrosine residue in the active site (see picture). As the modified enzyme was completely inactive until irradiated with UV light, temporal regulation of polymerase activity was possible.}, number={32}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Chou, Chungjung and Young, Douglas D. and Deiters, Alexander}, year={2009}, pages={5950–5953} }
 @article{bereman_young_deiters_muddiman_2009, title={Development of a Robust and High Throughput Method for Profiling N-Linked Glycans Derived from Plasma Glycoproteins by NanoLC-FTICR Mass Spectrometry}, volume={8}, ISSN={["1535-3907"]}, DOI={10.1021/pr9002323}, abstractNote={Recent investigations continue to emphasize the importance of glycosylation in various diseases including cancer. In this work, we present a step-by-step protocol describing a method for N-linked glycan profiling of plasma glycoproteins by nanoflow liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). A large experimental space was initially explored and is described herein. Three internal standards were spiked into the sample and provided normalization of plasma glycan abundance across different experimental conditions. Incubation methods and times and the effect of NP40 detergent on glycan abundance were explored. It was found that an 18-h incubation with no detergent led to the greatest ion abundance; however, data could be obtained in less than one day from raw plasma samples utilizing microwave irradiation or shorter incubation periods. The intersample precision of three different glycans was less than 5.5% (RSD) when the internal standards were added prior to the initial processing step. The high mass measurement accuracy (<3 ppm) afforded by the FTICR mass spectrometer provided confident identifications of several glycan species.}, number={7}, journal={JOURNAL OF PROTEOME RESEARCH}, author={Bereman, Michael S. and Young, Douglas D. and Deiters, Alexander and Muddiman, David C.}, year={2009}, month={Jul}, pages={3764–3770} }
 @article{nguyen_lusic_neumann_kapadnis_deiters_chin_2009, title={Genetic Encoding and Labeling of Aliphatic Azides and Alkynes in Recombinant Proteins via a Pyrrolysyl-tRNA Synthetase/tRNA(CUA) Pair and Click Chemistry}, volume={131}, ISSN={["0002-7863"]}, DOI={10.1021/ja900553w}, abstractNote={We demonstrate that an orthogonal Methanosarcina barkeri MS pyrrolysyl-tRNA synthetase/tRNA(CUA) pair directs the efficient, site-specific incorporation of N6-[(2-propynyloxy)carbonyl]-L-lysine, containing a carbon-carbon triple bond, and N6-[(2-azidoethoxy)carbonyl]-L-lysine, containing an azido group, into recombinant proteins in Escherichia coli. Proteins containing the alkyne functional group are labeled with an azido biotin and an azido fluorophore, via copper catalyzed [3+2] cycloaddition reactions, to produce the corresponding triazoles in good yield. The methods reported are useful for the site-specific labeling of recombinant proteins and may be combined with mutually orthogonal methods of introducing unnatural amino acids into proteins as well as with chemically orthogonal methods of protein labeling. This should allow the site specific incorporation of multiple distinct probes into proteins and the control of protein topology and structure by intramolecular orthogonal conjugation reactions.}, number={25}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Nguyen, Duy P. and Lusic, Hrvoje and Neumann, Heinz and Kapadnis, Prashant B. and Deiters, Alexander and Chin, Jason W.}, year={2009}, month={Jul}, pages={8720-+} }
 @misc{deiters_2009, title={Light activation as a method of regulating and studying gene expression}, volume={13}, ISSN={["1879-0402"]}, DOI={10.1016/j.cbpa.2009.09.026}, abstractNote={Recently, several advances have been made in the activation and deactivation of gene expression using light. These developments are based on the application of small molecule inducers of gene expression, antisense- or RNA interference-mediated gene silencing, and the photochemical control of proteins regulating gene function. The majority of the examples employ a classical 'caging technology', through the chemical installation of a light-removable protecting group on the biological molecule (small molecule, oligonucleotide, or protein) of interest and rendering it inactive. UV light irradiation then removes the caging group and activates the molecule, enabling control over gene activity with high spatial and temporal resolution.}, number={5-6}, journal={CURRENT OPINION IN CHEMICAL BIOLOGY}, author={Deiters, Alexander}, year={2009}, month={Dec}, pages={678–686} }
 @article{edwards_young_deiters_2009, title={Light-Activated Cre Recombinase as a Tool for the Spatial and Temporal Control of Gene Function in Mammalian Cells}, volume={4}, ISSN={["1554-8937"]}, DOI={10.1021/cb900041s}, abstractNote={Cre recombinase catalyzes DNA exchange between two conserved lox recognition sites. The enzyme has extensive biological application, from basic cloning to engineering knock-out and knock-in organisms. Widespread use of Cre is due to its simplicity and effectiveness, but the enzyme and the recombination event remain difficult to control with high precision. To obtain such control we report the installation of a light-responsive o-nitrobenzyl caging group directly in the catalytic site of Cre, inhibiting its activity. Prior to irradiation, caged Cre is completely inactive, as demonstrated both in vitro and in mammalian cell culture. Exposure to non-damaging UVA light removes the caging group and restores recombinase activity. Tight spatio-temporal control over DNA recombination is thereby achieved.}, number={6}, journal={ACS CHEMICAL BIOLOGY}, author={Edwards, Wesleigh F. and Young, Douglas D. and Deiters, Alexander}, year={2009}, month={Jun}, pages={441–445} }
 @article{young_garner_yoder_deiters_2009, title={Light-activation of gene function in mammalian cells via ribozymes}, ISSN={1359-7345 1364-548X}, url={http://dx.doi.org/10.1039/b819375d}, DOI={10.1039/b819375d}, abstractNote={A ribozyme based gene control element enabled the spatio-temporal regulation of gene function in mammalian cell culture with light.}, number={5}, journal={Chem. Commun.}, publisher={Royal Society of Chemistry (RSC)}, author={Young, Douglas D. and Garner, R. Aaron and Yoder, Jeffrey A. and Deiters, Alexander}, year={2009}, pages={568–570} }
 @article{young_teske_deiters_2009, title={Open-Vessel Microwave-Mediated [2+2+2]-Cyclotrimerization Reactions}, ISSN={["1437-210X"]}, DOI={10.1055/s-0029-1218149}, abstractNote={[2+2+2]-Cyclotrimerization reactions often suffer from low reaction rates and low chemoselectivity. We are reporting a solution to both problems through the use of open-vessel conditions for microwave-mediated cyclotrimerization reactions.}, number={22}, journal={SYNTHESIS-STUTTGART}, author={Young, Douglas D. and Teske, Jesse A. and Deiters, Alexander}, year={2009}, month={Nov}, pages={3785–3790} }
 @article{young_govan_lively_deiters_2009, title={Photochemical Regulation of Restriction Endonuclease Activity}, volume={10}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.200900090}, abstractNote={Abstract}, number={10}, journal={CHEMBIOCHEM}, author={Young, Douglas D. and Govan, Jeane M. and Lively, Mark O. and Deiters, Alexander}, year={2009}, month={Jul}, pages={1612–1616} }
 @article{young_lusic_lively_deiters_2009, title={Restriction enzyme-free mutagenesis via the light regulation of DNA polymerization}, volume={37}, number={8}, journal={Nucleic Acids Research}, author={Young, D. D. and Lusic, H. and Lively, M. O. and Deiters, A.}, year={2009} }
 @article{edwards_young_deiters_2009, title={The effect of microwave irradiation on DNA hybridization}, volume={7}, ISSN={["1477-0539"]}, DOI={10.1039/b903609a}, abstractNote={The effect of microwave irradiation on DNA/DNA hybridization has been studied under controlled power and temperature conditions. It was discovered that microwave irradiation led to the melting of double-stranded deoxyoligonucleotides well below their thermal melting temperature and independent of the length of the deoxyoligonucleotides. These observations indicate a specific interaction of microwaves with DNA, and have important implications in the chemical or enzymatic processing of DNA under microwave heating.}, number={12}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Edwards, Wesleigh F. and Young, Douglas D. and Deiters, Alexander}, year={2009}, pages={2506–2508} }
 @article{teske_deiters_2008, title={A cyclotrimerization route to cannabinoids}, volume={10}, ISSN={["1523-7052"]}, DOI={10.1021/ol800589e}, abstractNote={Three members of the cannabinoid class, cannabinol, cannabinol methyl ether, and cannabinodiol, were synthesized using a microwave-mediated [2 + 2 + 2] cyclotrimerization reaction as the key step. This approach provides a high level of synthetic flexibility allowing for the facile synthesis of cannabinoid analogues.}, number={11}, journal={ORGANIC LETTERS}, author={Teske, Jesse A. and Deiters, Alexander}, year={2008}, month={Jun}, pages={2195–2198} }
 @article{mciver_young_deiters_2008, title={A general approach to triphenylenes and azatriphenylenes: total synthesis of dehydrotylophorine and tylophorine}, ISSN={["1359-7345"]}, DOI={10.1039/b811068a}, abstractNote={A convergent and flexible synthesis of substituted triphenylenes, azatriphenylenes, and the cytotoxic alkaloids dehydrotylophorine and tylophorine has been developed.}, number={39}, journal={CHEMICAL COMMUNICATIONS}, author={McIver, Andrew and Young, Douglas D. and Deiters, Alexander}, year={2008}, pages={4750–4752} }
 @article{young_lusic_lively_yoder_deiters_2008, title={Gene Silencing in Mammalian Cells with Light-Activated Antisense Agents}, volume={9}, ISSN={1439-4227 1439-7633}, url={http://dx.doi.org/10.1002/cbic.200800627}, DOI={10.1002/cbic.200800627}, abstractNote={Detailed knowledge of the external regulation of gene func-tion is a fundamental necessity in order to annotate sequencedgenomes and to understand biological processes in single cellsand multicellular organisms. One of the most widely used ap-proaches for the down-regulation of specific genes is the ap-plication of antisense agents. Antisense agents are oligomersthat have the ability to hybridize sequence specificslly tomRNAs, inhibiting translation and potentially leading to mRNAdegradation through RNAse H recruitment.}, number={18}, journal={ChemBioChem}, publisher={Wiley}, author={Young, Douglas D. and Lusic, Hrvoje and Lively, Mark O. and Yoder, Jeffrey A. and Deiters, Alexander}, year={2008}, month={Dec}, pages={2937–2940} }
 @article{lusic_lively_deiters_2008, title={Light-activated deoxyguanosine: photochemical regulation of peroxidase activity}, volume={4}, ISSN={["1742-206X"]}, DOI={10.1039/b800166a}, abstractNote={Photochemical activation of a deoxyribozyme with peroxidase activity was achieved by the synthesis and incorporation of a caged deoxyguanosine.}, number={6}, journal={MOLECULAR BIOSYSTEMS}, author={Lusic, Hrvoje and Lively, Mark O. and Deiters, Alexander}, year={2008}, pages={508–511} }
 @article{young_deiters_2008, title={Light-regulated RNA-small molecule interactions}, volume={9}, ISSN={["1439-4227"]}, DOI={10.1002/cbic.200800051}, abstractNote={The development of light-regulated processes represents a noninvasive means to exert a high level of spatial and temporal control over a chemical or biological system.[1] The ability to light regulate the activity of biologically relevant molecules by the installation of photolabile protecting groups that are removed upon irradiation with ultraviolet light has been demonstrated numerous times in this context. Examples of this approach include the regulation of gene expression,[2] protein production,[3] protein function,[4] as well as antisense,[5] DNA,[6] and RNA function.[7] Other caged biologically relevant small molecules include ATP, Ca2+, theophylline, and fatty acids.[8] However, the decaging process only allows for the irreversible activation or deactivation of the system under study, thus limiting the scope of its utility.}, number={8}, journal={CHEMBIOCHEM}, author={Young, Douglas D. and Deiters, Alexander}, year={2008}, month={May}, pages={1225–1228} }
 @article{young_edwards_lusic_lively_deiters_2008, title={Light-triggered polymerase chain reaction}, ISSN={["1364-548X"]}, DOI={10.1039/b715152g}, abstractNote={Photochemical control of the polymerase chain reaction has been achieved through the incorporation of light-triggered nucleotides into DNA.}, number={4}, journal={CHEMICAL COMMUNICATIONS}, author={Young, Douglas D. and Edwards, Wesleigh F. and Lusic, Hrvoje and Lively, Mark O. and Deiters, Alexander}, year={2008}, pages={462–464} }
 @article{young_nichols_kelly_deiters_2008, title={Microwave activation of enzymatic catalysis}, volume={130}, ISSN={["0002-7863"]}, DOI={10.1021/ja802404g}, abstractNote={Microwave irradiation can be used to regulate biocatalysis. Herein, the utilization of hyperthermophilic enzymes in a microwave reactor is reported. While these enzymes are inactive at low temperatures, they can be activated with microwave irradiation. To the best of our knowledge, this is the first illustration of a specific microwave effect in enzymatic catalysis.}, number={31}, journal={JOURNAL OF THE AMERICAN CHEMICAL SOCIETY}, author={Young, Douglas D. and Nichols, Jason and Kelly, Robert M. and Deiters, Alexander}, year={2008}, month={Aug}, pages={10048-+} }
 @article{young_torres-kolbus_deiters_2008, title={Microwave-assisted synthesis of unnatural amino acids}, volume={18}, ISSN={["0960-894X"]}, DOI={10.1016/j.bmcl.2008.09.025}, abstractNote={Microwave irradiation has been proven to be a useful tool in the rapid assembly of racemic unnatural amino acids in only two steps. Additional benefits of this methodology are the commercial availability of the inexpensive starting materials and the high yields and high purities of the final amino acid products.}, number={20}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Young, Douglas D. and Torres-Kolbus, Jessica and Deiters, Alexander}, year={2008}, month={Oct}, pages={5478–5480} }
 @article{teske_deiters_2008, title={Microwave-mediated Nickel-catalyzed cyclotrimerization reactions: Total synthesis of illudinine}, volume={73}, ISSN={["1520-6904"]}, DOI={10.1021/jo7020955}, abstractNote={Rapid and efficient [2 + 2 + 2] cyclotrimerization reactions were discovered through the application of microwave irradiation in conjunction with a Ni(CO)(2)(PPh(3))(2) catalyst. This enables the facile construction of highly substituted indane, isoindoline, and tetraline core structures. The developed microwave-mediated Ni-catalyzed cyclotrimerization reaction was employed as the key step in a concise synthesis of the isoquinoline natural product illudinine. This represents the first example of a Ni-catalyzed cyclotrimerization reaction in total synthesis.}, number={1}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Teske, Jesse A. and Deiters, Alexander}, year={2008}, month={Jan}, pages={342–345} }
 @article{sripada_teske_deiters_2008, title={Phenanthridine synthesis via [2+2+2] cyclotrimerization reactions}, volume={6}, ISSN={["1477-0520"]}, DOI={10.1039/b716519f}, abstractNote={A concise synthesis of phenanthridines via a microwave-assisted [2+2+2] cyclotrimerization reaction has been developed.}, number={2}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Sripada, Lakshminath and Teske, Jesse A. and Deiters, Alexander}, year={2008}, pages={263–265} }
 @article{gumireddy_young_xiong_hogenesch_huang_deiters_2008, title={Small-molecule inhibitors of microRNA miR-21 function}, volume={47}, ISSN={["1521-3773"]}, DOI={10.1002/anie.200801555}, abstractNote={MicroRNAs (miRNAs) have recently emerged as an important class of gene regulators, and their misregulation has been linked to a variety of cancers. Small molecule inhibitors of miRNAs would be important tools to elucidate the detailed mechanisms of miRNA function and provide lead structures for the development of new therapeutics. We are reporting a cellular screen for miRNA pathway inhibitors and the first small molecule modifiers of miRNA function.}, number={39}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Gumireddy, Kiranmai and Young, Douglas D. and Xiong, Xin and Hogenesch, John B. and Huang, Qihong and Deiters, Alexander}, year={2008}, pages={7482–7484} }
 @article{lusic_gustilo_vendeix_kaiser_delaney_graham_moye_cantara_agris_deiters_2008, title={Synthesis and investigation of the 5-formylcytidine modified, anticodon stem and loop of the human mitochondrial tRNA(Met)}, volume={36}, ISSN={["1362-4962"]}, DOI={10.1093/nar/gkn703}, abstractNote={Human mitochondrial methionine transfer RNA (hmtRNAMetCAU) has a unique post-transcriptional modification, 5-formylcytidine, at the wobble position-34 (f5C34). The role of this modification in (hmtRNAMetCAU) for the decoding of AUA, as well as AUG, in both the peptidyl- and aminoacyl-sites of the ribosome in either chain initiation or chain elongation is still unknown. We report the first synthesis and analyses of the tRNA's anticodon stem and loop domain containing the 5-formylcytidine modification. The modification contributes to the tRNA's anticodon domain structure, thermodynamic properties and its ability to bind codons AUA and AUG in translational initiation and elongation.}, number={20}, journal={NUCLEIC ACIDS RESEARCH}, author={Lusic, Hrvoje and Gustilo, Estella M. and Vendeix, Franck A. P. and Kaiser, Rob and Delaney, Michael O. and Graham, William D. and Moye, Virginia A. and Cantara, William A. and Agris, Paul F. and Deiters, Alexander}, year={2008}, month={Nov}, pages={6548–6557} }
 @article{zou_young_cruz-montanez_deiters_2008, title={Synthesis of Anthracene and Azaanthracene Fluorophores via [2+2+2] Cyclotrimerization Reactions}, volume={10}, ISSN={["1523-7052"]}, DOI={10.1021/ol8019549}, abstractNote={A highly convergent [2+2+2] cyclotrimerization approach to anthracenes and 2-azaanthracenes has been developed. It allows for the facile introduction of the anthracene moiety on alkyne and nitrile bearing molecules and the rapid construction of compound arrays. This is showcased in the assembly of a collection of fluorophores and their photochemical evaluation.}, number={20}, journal={ORGANIC LETTERS}, author={Zou, Yan and Young, Douglas D. and Cruz-Montanez, Alejandra and Deiters, Alexander}, year={2008}, month={Oct}, pages={4661–4664} }
 @article{young_deiters_2007, title={A general approach to chemo- and regioselective cyclotrimerization reactions}, volume={46}, ISSN={["1433-7851"]}, DOI={10.1002/anie.200700802}, abstractNote={Microwave-ready heterocycles: Cobalt-catalyzed [2+2+2] cyclotrimerization of nitrile derivatives with diynes anchored to a solid support under microwave irradiation provides a universal approach to pyridine, pyridone, and iminopyridine products. The reaction is completely chemo- and regioselective, and the products are obtained in excellent yield and high purity.}, number={27}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Young, Douglas D. and Deiters, Alexander}, year={2007}, pages={5187–5190} }
 @article{young_sripada_deiters_2007, title={Microwave-assisted solid-supported alkyne cyclotrimerization reactions for combinatorial chemistry}, volume={9}, ISSN={["1520-4766"]}, DOI={10.1021/cc070068b}, abstractNote={ADVERTISEMENT RETURN TO ISSUEReportNEXTMicrowave-Assisted Solid-Supported Alkyne Cyclotrimerization Reactions for Combinatorial ChemistryDouglas D. Young, Lakshminath Sripada, and Alexander DeitersView Author Information Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204 Cite this: J. Comb. Chem. 2007, 9, 5, 735–738Publication Date (Web):July 21, 2007Publication History Received4 May 2007Published online21 July 2007Published inissue 1 September 2007https://doi.org/10.1021/cc070068bCopyright © 2007 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views723Altmetric-Citations35LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (243 KB) Supporting Info (1)»Supporting Information Supporting Information SUBJECTS:Aromatic compounds,Electromagnetic radiation,Hydrocarbons,Irradiation,Reactivity Get e-Alerts}, number={5}, journal={JOURNAL OF COMBINATORIAL CHEMISTRY}, author={Young, Douglas D. and Sripada, Lakshminath and Deiters, Alexander}, year={2007}, pages={735–738} }
 @article{lusic_young_lively_deiters_2007, title={Photochemical DNA activation}, volume={9}, ISSN={["1523-7052"]}, DOI={10.1021/ol070455u}, abstractNote={A new photocaged nucleoside was synthesized and incorporated into DNA with the use of standard synthesis conditions. This approach enabled the disruption of specific H-bonds and allowed for the analysis of their contribution to the activity of a DNAzyme. Brief irradiation with nonphotodamaging UV light led to rapid decaging and almost quantitative restoration of DNAzyme activity. The developed strategy has the potential to find widespread application in the light-induced regulation of oligonucleotide function.}, number={10}, journal={ORGANIC LETTERS}, author={Lusic, Hrvoje and Young, Douglas D. and Lively, Mark O. and Deiters, Alexander}, year={2007}, month={May}, pages={1903–1906} }
 @article{young_deiters_2007, title={Photochemical activation of protein expression in bacterial cells}, volume={46}, ISSN={["1521-3773"]}, DOI={10.1002/anie.200700057}, abstractNote={Small-molecule-inducible gene-expression systems are available in a variety of cell types including bacterial cells, yeast cells, and mammalian cells. They have been used for conditional protein expression in higher organisms ranging from plants to mice. These systems are typically composed of a natural receptor taken from one organism and transferred into a second organism, in conjunction with a natural or unnatural small-molecule ligand that is orthogonal to all endogenous molecules of the organism of interest. Exposure of the organism to the small molecule typically activates gene expression, a process that has found application in the production of recombinant proteins, the programing of biological processes, and the study of gene function. Although this technique enables temporal control over gene function on a minute-to-hour timescale, it does not permit spatial control. A highly efficient way to simultaneously achieve spatial and temporal control over biological processes is the application of photocaging. The term “caging” defines the installation of a photoremovable group on a biologically active molecule, thus rendering the molecule inactive. Caging groups have been installed on small molecules, oligonucleotides, peptides, and proteins. Irradiation with UV light removes the caging group and restores biological activity. Recently, this approach has been applied to the light activation of small-molecule inducers of protein expression. Both reported systems, that is, the doxycycline and the nuclear hormone (for example, estradiol) conditional-geneexpression systems, are restricted to eukaryotic cells. Here we report a light-inducible gene-expression system which can be used in bacterial cells, plants, and mammalian organisms. It is based on the lactose (lac) repressor which binds to the lac operator (lacO), thereby inhibiting RNA polymerase from performing gene transcription. In presence of the small-molecule effector isopropyl-b-d-thio-galactoside (IPTG), the repressor is released from the DNA through an allosteric binding event, which results in a conformational change and leads to gene expression (Figure 1). The crystal structure of the LacI/IPTG complex (Protein Data Bank file no. 1LBH) reveals interactions between the small molecule and the protein in a tight binding pocket, as well as four essential hydrogen bonds between the 4-OH group and Arg197, the 3-OH group and Arg197, and also the 2-OH group and Asp274 and Asn246 (see the Supporting Information). We speculated that disruption of the hydrogen-bond network through the installation of a sterically demanding caging group on IPTG would inhibit the formation of the LacI/IPTG complex and thereby inhibit gene expression. If the installed group is removable through irradiation with UV light, IPTG can be generated in a spatiotemporal manner, thereby enabling spatiotemporal control over protein expression. In order to achieve this, the caged IPTG 1 was synthesized in a single step (78% yield) by the reaction of IPTG with 6-nitropiperonal (see the Experimental Section), which furnished selective dioxolan formation at the 4and 6-hydroxy groups. This is in accordance with the results of NMR experiments and previous observations in similar reactions. The caged IPTG 1 is nontoxic to bacterial cells and no degradation was observed under physiological conditions. Irradiation of an aqueous solution of 1 ( 0.5 mm, e365= 4533 cm m ) with nonphotodamaging UV light (handheld UV lamp, 365 nm, 0.5 Wcm ) for 5 min leads to quantitative formation of the ester 2, as a 1:1 mixture of regioisomers (4-OH/6-OH, Scheme 1 shows the 4-OH ester). The half life for the conversion 1!2 after irradiation depends on the concentration of 1 and amounts to 11 s at a concentration of 0.1 mm, 5.1 min at 0.5 mm, or 11.8 min at 1.0 mm (see the Supporting Information). This facile photolytic conversion of a 1,3-dioxane is in remarkable contrast to previous observations with bromohydroxycoumarin caged diols. The quantum yield (f= 0.131) for the photochemical conversion of 1 into 2 has been determined by 3,4-dimethoxynitrobenzene actinometry. The ester 2 is stable in an aqueous solution; however, as observed for other carbohydrate esters, 2 is hydrolyzed to IPTG by the esterases found in a cellular environment (t1/2= 63 min 2 min, see the Supporting Information). The growth of bacterial cells exposed to 0.5 mm concentrations of 1 and 2 revealed that the compounds do not reduce growth rates, are nontoxic, and are easily taken up by the cells (see the Supporting Information). Figure 1. IPTG-induced expression of an open reading frame (ORF) through formation of the IPTG/lac repressor complex.}, number={23}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Young, Douglas D. and Deiters, Alexander}, year={2007}, pages={4290–4292} }
 @article{young_deiters_2007, title={Photochemical control of biological processes}, volume={5}, ISSN={["1477-0539"]}, DOI={10.1039/b616410m}, abstractNote={Photochemical regulation of biological processes offers a high level of control to study intracellular mechanisms with unprecedented spatial and temporal resolution. This report summarizes the advances made in recent years, focusing predominantly on the in vivo regulation of gene function using irradiation with UV light. The majority of the described applications entail the utilization of photocaging groups installed either on a small molecule modulator of biomolecular function or directly on a biological macromolecule itself.}, number={7}, journal={ORGANIC & BIOMOLECULAR CHEMISTRY}, author={Young, Douglas D. and Deiters, Alexander}, year={2007}, pages={999–1005} }
 @article{senaiar_teske_young_deiters_2007, title={Synthesis of indanones via solid-supported [2+2+2] cyclotrimerization}, volume={72}, ISSN={["0022-3263"]}, DOI={10.1021/jo7013565}, abstractNote={A new facile approach toward natural and unnatural indanones has been developed, featuring a solid-supported [2+2+2] cyclotrimerization as the key step. This strategy has been applied to the chemo- and regioselective assembly of indanone arrays and to the total synthesis of a recently isolated indanone marine natural product.}, number={20}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Senaiar, Ramesh S. and Teske, Jesse A. and Young, Douglas D. and Deiters, Alexander}, year={2007}, month={Sep}, pages={7801–7804} }
 @article{summerer_chen_wu_deiters_chin_schultz_2006, title={A genetically encoded fluorescent amino acid}, volume={103}, ISSN={["0027-8424"]}, DOI={10.1073/pnas.0603965103}, abstractNote={
            The ability to introduce fluorophores selectively into proteins provides a powerful tool to study protein structure, dynamics, localization, and biomolecular interactions both
            in vitro
            and
            in vivo
            . Here, we report a strategy for the selective and efficient biosynthetic incorporation of a low-molecular-weight fluorophore into proteins at defined sites. The fluorescent amino acid 2-amino-3-(5-(dimethylamino)naphthalene-1-sulfonamide)propanoic acid (dansylalanine) was genetically encoded in
            Saccharomyces cerevisiae
            by using an amber nonsense codon and corresponding orthogonal tRNA/aminoacyl-tRNA synthetase pair. This environmentally sensitive fluorophore was selectively introduced into human superoxide dismutase and used to monitor unfolding of the protein in the presence of guanidinium chloride. The strategy described here should be applicable to a number of different fluorophores in both prokaryotic and eukaryotic organisms, and it should facilitate both biochemical and cellular studies of protein structure and function.
          }, number={26}, journal={PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, author={Summerer, Daniel and Chen, Shuo and Wu, Ning and Deiters, Alexander and Chin, Jason W. and Schultz, Peter G.}, year={2006}, month={Jun}, pages={9785–9789} }
 @article{deiters_groff_ryu_xie_schultz_2006, title={A genetically encoded photocaged tyrosine}, volume={45}, ISSN={["1521-3773"]}, DOI={10.1002/anie.200600264}, abstractNote={Activating proteins with light: A photocaged tyrosine was genetically encoded in E. coli in response to the amber codon TAG. Substitution of Tyr 503 in the active site of β-galactosidase allowed photoactivation of this enzyme in vitro or directly in bacteria with 360-nm light. This method should allow photoregulation of the activity of a variety of biological processes including transcription, signal transduction, and cellular trafficking.}, number={17}, journal={ANGEWANDTE CHEMIE-INTERNATIONAL EDITION}, author={Deiters, A and Groff, D and Ryu, YH and Xie, JM and Schultz, PG}, year={2006}, pages={2728–2731} }
 @article{lusic_deiters_2006, title={A new photocaging group for aromatic N-heterocycles}, ISSN={["1437-210X"]}, DOI={10.1055/s-2006-942424}, abstractNote={Biologically relevant nitrogen-containing heterocycles were photo-protected using an NPOM caging group that is stable under physiological conditions but readily decages under irradiation with non-photodamaging UV light.}, number={13}, journal={SYNTHESIS-STUTTGART}, author={Lusic, Hrvoje and Deiters, Alexander}, year={2006}, month={Jul}, pages={2147–2150} }
 @article{deiters_yoder_2006, title={Conditional transgene and gene targeting methodologies in zebrafish}, volume={3}, journal={Zebrafish}, author={Deiters, A. and Yoder, J. A.}, year={2006}, pages={415–429} }
 @misc{deiters_pettersson_martin_2006, title={General strategy for the syntheses of corynanthe, tacaman, and oxindole alkaloids}, volume={71}, ISSN={["1520-6904"]}, DOI={10.1021/jo061032t}, abstractNote={We report herein the total synthesis of the corynanthe alkaloid dihydrocorynantheol and the formal syntheses of the indole alkaloids tacamonine, rhynchophylline, and hirsutine. The strategies for assembling the corynanthe and tacaman skeletal frameworks comprised of both the classical ABD --> ABCD and ABC --> ABCD approaches wherein the variously substituted piperidinone D-rings were formed via ring-closing metathesis (RCM) followed by a 1,4-addition to introduce the requisite side chain at C(15). Since 1,4-additions to alpha,beta-unsaturated lactams represent an underdeveloped field, we conducted a series of studies with two unsaturated lactams employing organocuprates and metal enolates as the nucleophiles. These studies revealed that organocuprates derived from Grignard reagents and either stoichiometric amounts of CuCN or catalytic amounts of CuBr.DMS complex are excellent nucleophiles for such additions; TMSCl was a crucial additive for optimizing these reactions. The anion derived from ethyl 1,3-dithiolane-2-carboxylate was also an excellent nucleophile in these 1,4-additions, although the stereochemistry of such 1,4-additions to carboline-derived, unsaturated lactams was sensitive to substitution on the indole nitrogen atom. The ABD --> ABCD approach to these alkaloids featured a novel one-pot sequence of an RCM reaction and a zirconocene-catalyzed carbomagnesation followed by a second RCM to generate the D-ring.}, number={17}, journal={JOURNAL OF ORGANIC CHEMISTRY}, author={Deiters, Alexander and Pettersson, Martin and Martin, Stephen F.}, year={2006}, month={Aug}, pages={6547–6561} }
 @article{young_deiters_2006, title={Photochemical hammerhead ribozyme activation}, volume={16}, ISSN={["1464-3405"]}, DOI={10.1016/j.bmcl.2006.02.034}, abstractNote={We report the light-activation of allosteric cis and trans acting ribozymes via decaging of a small organic molecule ligand. To achieve this effectively, we introduce an optimized N-caging group based on a nitrobenzyl core structure. This approach can potentially be employed toward a light-induced control of gene function.}, number={10}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Young, DD and Deiters, A}, year={2006}, month={May}, pages={2658–2661} }
 @article{senaiar_young_deiters_2006, title={Pyridines via solid-supported [2+2+2] cyclotrimerization}, DOI={10.1039/b515901f}, abstractNote={The formation of pyridines via a crossed [2 + 2 + 2] cycloaddition has been achieved on a solid-support for the first time.}, number={12}, journal={Chemical Communications (Cambridge, England)}, author={Senaiar, R. S. and Young, D. D. and Deiters, A.}, year={2006}, pages={1313–1315} }
 @article{young_senaiar_deiters_2006, title={Solid-supported [2+2+2] cyclotrimerizations}, volume={12}, ISSN={["0947-6539"]}, DOI={10.1002/chem.200501360}, abstractNote={Abstract}, number={21}, journal={CHEMISTRY-A EUROPEAN JOURNAL}, author={Young, Douglas D. and Senaiar, Ramesh S. and Deiters, Alexander}, year={2006}, month={Jul}, pages={5563–5568} }
 @misc{deiters_martin_2004, title={Synthesis of oxygen- and nitrogen-containing heterocycles by ring-closing metathesis}, volume={104}, ISSN={["1520-6890"]}, DOI={10.1021/cr0200872}, abstractNote={ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Oxygen- and Nitrogen-Containing Heterocycles by Ring-Closing MetathesisAlexander Deiters and Stephen F. MartinView Author Information Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, and Department of Chemistry and Biochemistry, The University of Texas, Austin, Texas 78712 Cite this: Chem. Rev. 2004, 104, 5, 2199–2238Publication Date (Web):April 27, 2004Publication History Received16 October 2003Published online27 April 2004Published inissue 1 May 2004https://doi.org/10.1021/cr0200872Copyright © 2004 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views12619Altmetric-Citations1164LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (1 MB) Get e-AlertsSUBJECTS:Catalysts,Cyclization,Ethers,Lactones,Metathesis Get e-Alerts}, number={5}, journal={CHEMICAL REVIEWS}, author={Deiters, A and Martin, SF}, year={2004}, month={May}, pages={2199–2238} }