@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{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} }