Hybrid Antibiotics Targeting the Bacterial Ribosome.

ABSTRACT: Antimicrobial resistance remains a formidable challenge to modern medicine, with bacterial resistance mechanisms increasingly eroding the utility of clinically important antibiotics. While recent efforts have expanded the antibacterial pipeline, the development of resistance in priority pathogens continues to exceed the pace of new drug development. One emerging strategy to overcome resistance is the rational design of hybrid antibiotics that engage multiple binding sites. Here we describe the design, synthesis, and microbiological and structural characterization of hybrid antibiotics of azithromycin, tedizolid, and chloramphenicol that span the peptidyltransferase center (PTC) and nascent peptide exit tunnel (NPET) in the bacterial ribosome. We characterize the binding of four such hybrid

SUBMITTER: Yeon SK 

PROVIDER: S-EPMC12670282 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature