Design, synthesis, and characterization of dipeptide isostere containing cis-epoxide for the irreversible inactivation of HIV protease

Abstract A novel isostere was designed for the inactivation of HIV protease on the basis of mechanistic and structural information. Key factors of the inactivator are the cis -epoxide for the nucleophilic addition of the active site aspartic residue and two amide carbonyls at P2 and P1' for the formation of the hydrogen-bondings with an essential structural water molecule. Novel isostere was designed for the inactivation of HIV protease on the basis of mechanistic and structural information. The key factors of the inactivators are the cis -epoxide for the nucleophilic addition of the aspartic residue at the active site and two amide carbonyls at P2 and P1′ for the formation of the hydrogen-bondings with an essential structural water molecule.