A Vancomycin-Templated DNA-Encoded Library for Combating Drug-Resistant Bacteria

作者：Dongliang Guan, Jiaxiang Liu, Feifei Chen, Jian Li, Xiaowen Wang, Weiwei Lu, Yanrui Suo, Feng Tang, Lefu Lan, Xiaojie Lu, Wei Huang · 发表于：Journal of Medicinal Chemistry · 年份：2024 · DOI：10.1021/acs.jmedchem.3c02197 · 被引用次数：11 · 研究领域：Antimicrobial Peptides and Activities、Chemical Synthesis and Analysis、Bacteriophages and microbial interactions

It is an urgent need to tackle the global crisis of multidrug-resistant bacterial infections. We report here an innovative strategy for large-scale screening of new antibacterial agents using a whole bacteria-based DNA-encoded library (DEL) of vancomycin derivatives via peripheral modifications. A bacterial binding affinity assay was established to select the modification fragments in high-affinity compounds. The optimal resynthesized derivatives demonstrated excellently enhanced activity against various resistant bacterial strains and provided useful structures for vancomycin derivatization. This work presents the new concept in a natural product-templated DEL and in antibiotic discovery through bacterial affinity screening, which promotes the fight against drug-resistant bacteria.