BPS 2025
Enablement of Late-Stage Functionalization and High-Throughput Parallel Chemistry for Efficient Peptide Optimization
Akshay Shah
Director of Chemistry, Pinnacle Medicines
ABSTRACT
Late-stage-enabling, high-throughput chemistries have been gaining momentum in the peptide drug discovery campaigns as chemists strive for fuller, shorter and fewer design-test-make cycles to optimize chemical leads into clinical candidates. A balance between the throughput (parallel vs singleton execution) and the stage (late vs early) of diversity introduction is necessary as they often run counter to one another. It is up to the ultimate objective one hopes to achieve that may tilt the balance in the favor of one over the other. The presentation will highlight: 1) photoredox-catalyzed decarboxylative Giese additions to dehydroalanine derivatives; and 2) Suzuki cross-couplings with 4-Br phenylalanine derivatives and draw focus on strategies to maximize speed and efficiency for diversity introduction.
BIO
Dr. Akshay Shah is an experienced medicinal chemists with 10 years of combined drug discovery experience across modalities that include small molecules and peptides. He has authored 15+ peer-reviewed publications and hold inventorship on 10+ patents while frequently providing peer-reviews to top journals. Upon completion of PhD at Indiana University, Bloomington in 2014 focusing on natural product synthesis and subsequent postdoctoral stint with renowned chemist Prof. K. C. Nicolaou at Rice University, Dr. Shah joined medicinal chemistry department at Pfizer as a senior Scientist and focused on development of novel, high-throughput parallel chemistries for SAR expansions. In 2017, Dr. Shah moved to Merck Research Labs in West Point, PA where he made key contributions to identification of small molecule clinical candidate. His interest in peptide discovery led him to Johnson & Johnson in 2021 as a Principal Scientist where Dr. Shah led medicinal chemistry efforts on multiple programs delivering on key discovery milestones. Dr. Shah is currently the Director of Chemistry at Pinnacle Medicines where his efforts built and advanced a deep discovery chemistry portfolio focused on cyclic peptides.