@article{massaro_pierce_2023, title={3-Component Approach to 1,5-Dihydro-2<i>H</i>-pyrrol-2-one Heterocycles}, volume={100}, ISSN={["2333-3553"]}, DOI={10.15227/orgsyn.100.0418}, journal={ORGANIC SYNTHESES}, author={Massaro, Nicholas P. and Pierce, Joshua G.}, year={2023}, pages={418-+} }
 @article{moody_brown_massaro_patel_agarwalla_simpson_brown_zheng_pierce_brudno_2022, title={Restoring Carboxylates on Highly Modified Alginates Improves Gelation, Tissue Retention and Systemic Capture}, volume={138}, ISSN={1742-7061}, url={http://dx.doi.org/10.1016/j.actbio.2021.10.046}, DOI={10.1016/j.actbio.2021.10.046}, abstractNote={Alginate hydrogels are gaining traction for use in drug delivery, regenerative medicine, and as tissue engineered scaffolds due to their physiological gelation conditions, high tissue biocompatibility, and wide chemical versatility. Traditionally, alginate is decorated at the carboxyl group to carry drug payloads, peptides, or proteins. While low degrees of substitution do not cause noticeable mechanical changes, high degrees of substitution can cause significant losses to alginate properties including complete loss of calcium cross-linking. While most modifications used to decorate alginate deplete the carboxyl groups, we propose that alginate modifications that replenish the carboxyl groups could overcome the loss in gel integrity and mechanics. In this report, we demonstrate that restoring carboxyl groups during functionalization maintains calcium cross-links as well as hydrogel shear-thinning and self-healing properties. In addition, we demonstrate that alginate hydrogels modified to a high degree with azide modifications that restore the carboxyl groups have improved tissue retention at intramuscular injection sites and capture blood-circulating cyclooctynes better than alginate hydrogels modified with azide modifications that deplete the carboxyl groups. Taken together, alginate modifications that restore carboxyl groups could significantly improve alginate hydrogel mechanics for clinical applications. STATEMENT OF SIGNIFICANCE: Chemical modification of hydrogels provides a powerful tool to regulate cellular adhesion, immune response, and biocompatibility with local tissues. Alginate, due to its biocompatibility and easy chemical modification, is being explored for tissue engineering and drug delivery. Unfortunately, modifying alginate to a high degree of substitution consumes carboxyl group, which are necessary for ionic gelation, leading to poor hydrogel crosslinking. We introduce alginate modifications that restore the alginate's carboxyl groups. We demonstrate that modifications that reintroduce carboxyl groups restore gelation and improve gel mechanics and tissue retention. In addition to contributing to a basic science understanding of hydrogel properties, we anticipate our approach will be useful to create tissue engineered scaffolds and drug delivery platforms.}, journal={Acta Biomaterialia}, publisher={Elsevier BV}, author={Moody, CT and Brown, AE and Massaro, NP and Patel, AS and Agarwalla, PA and Simpson, AM and Brown, AC and Zheng, H and Pierce, JG and Brudno, Y}, year={2022}, month={Jan}, pages={208–217} }
 @article{pandit_palvai_massaro_pierce_brudno_2022, title={Tissue-reactive drugs enable materials-free local depots}, volume={343}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2022.01.023}, abstractNote={Local, sustained drug delivery of potent therapeutics holds promise for the treatment of a myriad of localized diseases while eliminating systemic side effects. However, introduction of drug delivery depots such as viscous hydrogels or polymer-based implants is highly limited in stiff tissues such as desmoplastic tumors. Here, we present a method to create materials-free intratumoral drug depots through Tissue-Reactive Anchoring Pharmaceuticals (TRAPs). TRAPs diffuse into tissue and attach locally for sustained drug release. In TRAPs, potent drugs are modified with ECM-reactive groups and then locally injected to quickly react with accessible amines within the ECM, creating local drug depots. We demonstrate that locally injected TRAPs create dispersed, stable intratumoral depots deep within mouse and human pancreatic tumor tissues. TRAPs depots based on ECM-reactive paclitaxel (TRAP paclitaxel) had better solubility than free paclitaxel and enabled sustained in vitro and in vivo drug release. TRAP paclitaxel induced higher tumoral apoptosis and sustained better antitumor efficacy than the free drug. By providing continuous drug access to tumor cells, this material-free approach to sustained drug delivery of potent therapeutics has the potential in a wide variety of diseases where current injectable depots fall short.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Pandit, Sharda and Palvai, Sandeep and Massaro, Nicholas P. and Pierce, Joshua G. and Brudno, Yevgeny}, year={2022}, month={Mar}, pages={142–151} }
 @misc{valdes-pena_massaro_lin_pierce_2021, title={Leveraging Marine Natural Products as a Platform to Tackle Bacterial Resistance and Persistence}, volume={54}, ISSN={["1520-4898"]}, url={https://doi.org/10.1021/acs.accounts.1c00007}, DOI={10.1021/acs.accounts.1c00007}, abstractNote={ConspectusAntimicrobial resistance to existing antibiotics represents one of the greatest threats to human health and is growing at an alarming rate. To further complicate treatment of bacterial infections, many chronic infections are the result of bacterial biofilms that are tolerant to treatment with antibiotics because of the presence of metabolically dormant persister cell populations. Together these threats are creating an increasing burden on the healthcare system, and a "preantibiotic" age is on the horizon if significant action is not taken by the scientific and medical communities. While the golden era of antibiotic discovery (1940s-1960s) produced most of the antibiotic classes in clinical use today, followed by several decades of limited development, there has been a resurgence in antibiotic drug discovery in recent years fueled by the academic and biotech sectors. Historically, great success has been achieved by developing next-generation variants of existing classes of antibiotics, but there remains a dire need for the identification of novel scaffolds and/or antimicrobial targets to drive future efforts to overcome resistance and tolerance. In this regard, there has been no more valuable source for the identification of antibiotics than natural products, with 69-77% of approved antibiotics either being such compounds or being derived from them.Our group has developed a program centered on the chemical synthesis and chemical microbiology of marine natural products with unusual structures and promising levels of activity against multidrug-resistant (MDR) bacterial pathogens. As we are motivated by preparing and studying the biological effects of these molecules, we are not initially pursuing a biological question but instead are allowing the observed phenotypes and activities to guide the ultimate project direction. In this Account, our recent efforts on the synoxazolidinone, lipoxazolidinone, and batzelladine natural products will be discussed and placed in the context of the field's greatest challenges and opportunities. Specifically, the synoxazolidinone family of 4-oxazolidinone-containing natural products has led to the development of several chemical methods to prepare antimicrobial scaffolds and has revealed compounds with potent activity as adjuvants to treat bacterial biofilms. Bearing the same 4-oxazolidinone core, the lipoxazolidinones have proven to be potent single-agent antibiotics. Finally, our synthetic efforts toward the batzelladines revealed analogues with activity against a number of MDR pathogens, highlighted by non-natural stereochemical isomers with superior activity and simplified synthetic access. Taken together, these studies provide several distinct platforms for the development of novel therapeutics that can add to our arsenal of scaffolds for preclinical development and can provide insight into the biochemical processes and pathways that can be targeted by small molecules in the fight against antimicrobial-resistant and -tolerant infections. We hope that this work will serve as inspiration for increased efforts by the scientific community to leverage synthetic chemistry and chemical microbiology toward novel antibiotics that can combat the growing crisis of MDR and tolerant bacterial infections.}, number={8}, journal={ACCOUNTS OF CHEMICAL RESEARCH}, publisher={American Chemical Society (ACS)}, author={Valdes-Pena, M. Alejandro and Massaro, Nicholas P. and Lin, You-Chen and Pierce, Joshua G.}, year={2021}, month={Apr}, pages={1866–1877} }
 @article{massaro_pierce_2021, title={Rapid synthesis of the core scaffold of crinane and haemanthamine through a multi-component approach}, volume={75}, ISSN={["1873-3581"]}, url={https://doi.org/10.1016/j.tetlet.2021.153201}, DOI={10.1016/j.tetlet.2021.153201}, abstractNote={A rapid synthesis of the core structures of crinane and haemanthamine has been developed, enabled by a multicomponent approach. This work constitutes a formal synthesis of crinane and sets the stage for access to both families of natural products and key analogues. A key highlight of the approach is the modularity of the core synthesis, overcoming existing challenges for these scaffolds and providing a path to explore site-selective oxidation to expand the scope of molecules accessible from common intermediates.}, journal={TETRAHEDRON LETTERS}, publisher={Elsevier BV}, author={Massaro, Nicholas P. and Pierce, Joshua G.}, year={2021}, month={Jul} }
 @article{massaro_pierce_2020, title={Stereoselective, Multicomponent Approach to Quaternary Substituted Hydroindole Scaffolds}, volume={22}, ISSN={["1523-7052"]}, url={https://doi.org/10.1021/acs.orglett.0c01650}, DOI={10.1021/acs.orglett.0c01650}, abstractNote={The Amaryllidaceae alkaloids have been a target of synthesis for decades due to their complex architectures and biological activity. A central feature of these natural product cores is a quaternary substituted hydroindole heterocycle. Building off the foundation of our previous multicomponent approach to highly functionalized pyrrolidinones, herein we report a highly convergent, diastereoselective, multicomponent approach to access the hydroindole cores present within crinine, haemanthamine, pretazettine, and various other bioactive alkaloids. These scaffolds are additionally useful as building blocks for druglike molecules and natural product like library generation.}, number={13}, journal={ORGANIC LETTERS}, publisher={American Chemical Society (ACS)}, author={Massaro, Nicholas P. and Pierce, Joshua G.}, year={2020}, month={Jul}, pages={5079–5084} }