Covalent Inhibitors Kinetics

This lecture discusses the kinetics of covalent inhibitors, focusing on compounds A and B. The instructor explains the two-step binding regimen of compound A and the direct alkylation inhibition mechanism of compound B. The lecture covers the derivation of second-order rate constants and specificity of binding. Various experiments to demonstrate the covalent nature of the inhibitors are explored, along with the interaction of the inhibitors with a small-molecule thiol. The session concludes with a scheme illustrating how compounds A and B interact with a cysteine within the protein, considering the impact of oxidation on non-covalent interactions.