Incorporation of a transition-state mimic into substrate
analogues
– has been one of the strategies
– used in the development of enzyme inhibitors
• Substitution of the scissile amide bond
– with nonhydrolyzable dipeptide isosteres
• in the appropriate sequence context has proved
– to be successful in the development of potent renin inhibitors.
• A number of such dipeptide isosteres
– inserted into a heptapeptide template spanning P4-P3’
– and which mimic the tetrahedral intermediate of peptide
hydrolysis
– have been evaluated.