Synthesis and in vitro enzyme activity of peptide derivatives of bacterialcell wall biosynthesis inhibitors

The enzyme diaminopimelate aminotransferase (DAP-AT) is a good potential ta rget for the design of novel antibacterial agents. We have synthesised a se ries of peptide hydrazines based on the structure of the natural substrate of DAP-AT. These compounds show varied inhibition properties in vitro vs. D AP-AT from E. coli as well as moderate antimicrobial activity vs. E. coli. Examination of the kinetics of inhibition reveals that hydrazine, as well a s the substituted hydrazino-peptides, shows two-phase slow-binding inhibiti on. Possible mechanisms for inhibition are discussed.