RATIONAL DESIGN OF POTENT CARBOXYLIC ACID BASED BISUBSTRATE INHIBITORS OF RAS FARNESYL PROTEIN TRANSFERASE

Abstract Bisubstrate analog inhibitors in which a substrate mimetic tripeptide is attached to a homologated farnesyl carboxylic acid were synthesized and evaluated for in vitro inhibition versus ras farnesyl protein transferase (FPT). Our results demonstrate that such bisubstrate analogs are potent inhibitors of FPT.