Events in organic chemistry.

Expanding the Toolbox for Characterizing Epigenetic Protein-Protein Interactions Mediated by Post-translational Modification

Post-translational modification of histone proteins, including lysine methylation and acylation, regulate gene expression through recruitment of reader proteins to the nucleosome. Dysregulation of these events is prevalent in a wide range of diseases, such that there is much interest in characterizing these modifications and their binding partners.  We have used both supramolecular chemistry and protein engineering approaches to study the protein-protein interactions that are mediated by these post-translational modifications and to develop new tools to sense them.

Chemical Tools that IMPACT Lipid Signaling

The fidelity of intracellular signaling pathways requires that cells control the production of signaling agents in space and in time. Phosphatidic acid (PA) is both a central phospholipid biosynthetic intermediate and a multifunctional lipid second messenger produced at several discrete subcellular locations. The modes of action of PA can differ based on upstream stimulus, biosynthetic source, and site of production. How cells regulate the local production of PA to direct diverse signaling outcomes remains elusive.

Catalysis enabled enantioselective syntheses of Islatravir

Abstract Body: Non-adherence is a major hurdle for the effective treatment of HIV, a global epidemic even after 30 years of medical advancements. Long-acting therapeutics have the potential to improve adherence through simplified regimens. One such investigational medication is MK-8591, a nucleoside reverse transcriptase translocation inhibitor with subnanomolar antiviral activity and a long intracellular half-life. To support this program, a world-class manufacturing synthesis which is robust, green, and sustainable was targeted.


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