Homo-cysteinyl peptide inhibitors of the L1 metallo-beta-lactamase, and SAR as determined by combinatorial library synthesis.

Homo-cysteinyl peptides were found to be more active than cysteinyl peptides toward L1 metallo-beta-lactamase as reversible competitive inhibitors. A combinatorial library of more than 90 homo-cysteinyl peptides was synthesized and screened for their inhibitory activity toward the L1 enzyme. A systematic structure-activity relationship analysis has revealed the preferred interaction groups for L1 conserved binding sites of beta-lactam substrates. The most active compound 95b, had a K(i) of 2.1 nM.