Identifying Oxacillinase-48 Carbapenemase Inhibitors Using DNA-Encoded Chemical Libraries.

ABSTRACT: Bacterial resistance to β-lactam antibiotics is largely mediated by β-lactamases, which catalyze the hydrolysis of these drugs and continue to emerge in response to antibiotic use. β-Lactamases that hydrolyze the last resort carbapenem class of β-lactam antibiotics (carbapenemases) are a growing global health threat. Inhibitors have been developed to prevent β-lactamase-mediated hydrolysis and restore the efficacy of these antibiotics. However, there are few inhibitors available for problematic carbapenemases such as oxacillinase-48 (OXA-48). A DNA-encoded chemical library approach was used to rapidly screen for compounds that bind and potentially inhibit OXA-48. Using this approach, a hit compound, CDD-97, was identified with submicromolar potency (K_i = 0.53 ± 0.0

SUBMITTER: Taylor DM 

PROVIDER: S-EPMC7673237 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature