Human defensin-inspired discovery of peptidomimetic antibiotics

Gan Luo; Jue Zhang; HanBin Wang; YaQi Sun; BaoLi Cheng; ZhiPeng Xu; Yan Zhang; Hui Li; WuYuan Lu; Elizabeta Nemeth; Tomas Ganz; XiangMing Fang

doi:10.1073/pnas.2117283119

Human defensin-inspired discovery of peptidomimetic antibiotics

Proc Natl Acad Sci U S A. 2022 Mar 8;119(10):e2117283119. doi: 10.1073/pnas.2117283119. Epub 2022 Mar 1.

Authors

Gan Luo¹, Jue Zhang¹, HanBin Wang¹, YaQi Sun¹, BaoLi Cheng¹, ZhiPeng Xu¹, Yan Zhang², Hui Li¹, WuYuan Lu³, Elizabeta Nemeth⁴, Tomas Ganz⁴, XiangMing Fang¹

Affiliations

¹ Department of Anesthesiology and Intensive Care, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
² National Clinical Research Center for Child Health, Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.
³ Key Laboratory of Medical Molecular Virology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
⁴ Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095.

Abstract

SignificanceWe report the development of peptidomimetic antibiotics derived from a natural antimicrobial peptide, human α-defensin 5. By engaging multiple bacterial targets, the lead compound is efficacious in vitro and in vivo against bacteria with highly inducible antibiotic resistance, promising a useful therapeutic agent for the treatment of infections caused by antibiotic-resistant bacteria.

Keywords: antimicrobial resistance; defensins; infections; peptidomimetic antibiotics.

MeSH terms

Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology
Defensins / chemistry*
Defensins / pharmacology
Drug Discovery / methods*
Gram-Negative Bacteria / drug effects
Humans
Microbial Sensitivity Tests
Molecular Structure
Peptidomimetics / chemistry*
Peptidomimetics / pharmacology
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Defensins
Peptidomimetics