Assay for drug discovery: Synthesis and testing of nitrocefin analogues for use as β-lactamase substrates

Tetracycline-Inactivating Enzymes

“…A detailed understanding of enzymatic and non-enzymatic degradation cascades for tetracycline and other antibiotics is critical for designing future generations of molecules that overcome these resistance mechanisms and diagnostic tools to detect active antibiotic-inactivating enzymes in clinical samples. In fact, the degradation mechanisms of beta-lactam antibiotics by beta-lactamase enzymes were fundamentally important to the design of fluorogenic and chromogenic probes used in clinical diagnostic applications ( O’Callaghan et al, 1972 ; Yu et al, 2012 ; Ghavami et al, 2015 ).…”

Arginine-containing peptides as potent inhibitors of VIM-2 metallo-β-lactamase

“…ACCEPTED MANUSCRIPT 24 was not only significantly weaker (16 M and 9 M for K I and Kˈ I , respectively), but also (stringently) reliant on the presence of the cysteine residues.…”

“…were synthesized and characterized according to the protocols documented recently [24]. Except for nitrocefin, UW-57 and UW-58, stock solutions (2 mM) of the -lactams were prepared in Hepes buffer (50 mM, pH 7.0).…”

The Canadian Institutes of Health Research response to antimicrobial resistance

“…The first team funded dealt with bacterial cell wall synthesis and is in the process of testing several potential inhibitors with the aim of identifying leads for novel antibiotics (10)(11)(12). The second team studied bacterial resistance to β-lactam antibiotics which led to multiple outcomes, including the design, synthesis and testing of new candidate inhibitors of metallo-β-lactamases, and the characterization of inhibition of key metallo β-lactamases targets by known compounds (13,14). The Canada/U.K.…”