2024-25 Frederick L. Hovde Distinguished Lecturer

 

Arun Ghosh

Ian P. Rothwell Distinguished Professor of Organic Chemistry and Medicinal Chemistry

James Tarpo Jr. and Margaret Tarpo Department of Chemistry

 

Thursday, October 24, 2024

WTHR 104
4:30-5:30 - Lecture
5:30 - Reception
Flyer available here

Nature-Inspired Biomolecules in Today's Medicine

Abstract

Our longstanding interest in the chemistry and biology of natural products brought a unique perspective in our design of molecular probes against enzyme and receptor drug targets.  We are particularly intrigued by the cyclic ether and cyclic acetal structural features of numerous bioactive natural products. The cyclic ether functionalities in these molecules are critically important for their bioactivity. Conceivably, the cyclic ether oxygen is positioned to make up to two hydrogen bonding interactions with target peptide or protein residues. To alleviate some of the inherent problems associated with peptide-based drugs, we began to design bioactive natural product-derived scaffolds and templates to mimic the biological mode of action of peptide bonds.  Our in-depth work in the design of therapeutically relevant enzyme inhibitors began to demonstrate the power and significance of this strategy.  In the context of our ongoing structure-based design of protease inhibitors for treatment of HIV/AIDS, BACE1 inhibitors for treatment of Alzheimer’s Disease, SARS-CoV-2 main protease inhibitor for treatment of COVID-19, and selective GRK5 inhibitors for the treatment of multiple myeloma, we have been developing a range of exceptionally potent, selective, and drug-like inhibitors for clinical development.  This presentation will feature novel design concepts, development tools, and general strategies for drug design and discovery.