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This lecture covers the concepts of enzyme inhibition, focusing on reversible and irreversible mechanisms. It discusses the modes of action of drugs, including suicide inactivators, and the design of transition-state analogs. The instructor presents examples of mechanism-based inhibitors and explains how they covalently inactivate enzymes. The lecture also delves into the targeted protein degradation strategy using PROTACs, leveraging the ubiquitin proteasome system. It explores the bifunctional nature of PROTACs, their mechanism of action, and their application as an anti-cancer strategy. Additionally, the lecture introduces the bump-hole method for protein-ligand engineering, highlighting the development of analog-sensitive kinase alleles for chemical genetics.
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