A Vancomycin-Templated DNA-Encoded Library for Combating Drug-Resistant Bacteria
Dongliang Guan, Jiaxiang Liu, Feifei Chen, Jian Li, Xiaowen Wang, Weiwei Lu, Yanrui Suo, Feng Tang, Lefu Lan, Xiaojie Lu, Weitong Huang
Abstract
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.