Synthesis and proteinase inhibitory properties of diphenyl phosphonate analogues of aspartic and glutamic acids

The synthesis of diphenyl phosphonate analogues of aspartic and glutamic acid, and their inhibitory activity against S. aureus V8 protease and granzyme B, is described. The study has revealed difficulties with protecting group compatibility in the synthesis of these analogues. Two analogues, Acetyl.AspP(OPh)2 and Acetyl.GluP(OPh)2 were found to function as irreversible inactivators of V8 proteinase, yet exhibit no activity against granzyme B.