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.
Sun
Qin
Q
Department of Chemistry, University of Virginia, McCormick Road, PO Box 400319, Charlottesville, 22904, USA.
Law
Andy
A
Crowder
Michael W
MW
Geysen
H Mario
HM
D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D003545:Cysteine; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases
D004791:Enzyme Inhibitors; D019151:Peptide Library; D010455:Peptides; D065093:beta-Lactamase Inhibitors; C088032:beta-lactamase L1; D001618:beta-Lactamases; D003545:Cysteine