Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria

Wenjing Zhang; Shuai Deng; Min Zhou; Jingcheng Zou; Jiayang Xie; Ximian Xiao; Ling Yuan; Zhemin Ji; Sheng Chen; Ruxin Cui; Zhengjie Luo; Guixue Xia; Runhui Liu

doi:10.1039/D2BM00587E

Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria†

Wenjing Zhang,

‡^a Shuai Deng,

‡^a Min Zhou,

*^a Jingcheng Zou,

^b Jiayang Xie,

^b Ximian Xiao,^b Ling Yuan,

^b Zhemin Ji,^b Sheng Chen,

^b Ruxin Cui,

^b Zhengjie Luo,

^b Guixue Xia^b and Runhui Liu

*^ab

Author affiliations

* Corresponding authors

^a State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China
E-mail: rliu@ecust.edu.cn, minzhou@ecust.edu.cn

^b Key Laboratory for Ultrafine Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism, Research Center for Biomedical Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237, China

Abstract

Extensive use of antibiotics accelerates the emergence of drug-resistant bacteria and related infections. Host defense peptides (HDPs) have been studied as promising and potential therapeutic candidates. However, their clinical applications of HDPs are limited due to their high cost of synthesis and low stability upon proteolysis. Therefore, HDP mimics have become a new approach to address the challenge of bacterial resistance. In this work, we design the amphiphilic peptoid polymers by mimicking the positively charged and hydrophobic structures of HDPs and synthesize a series of cyclic peptoid polymers efficiently via the polymerization on α-amino acid N-substituted glycine N-carboxyanhydrides (α-NNCAs) using 1,8-diazabicycloundec-7-ene (DBU) as the initiator. The optimal cyclic peptoid polymer, poly(Naeg_0.7Npfbg_0.3)₂₀, displays strong antibacterial activities against drug-resistant bacteria, but low hemolysis and cytotoxicity. In addition, the mode-of-action study indicates that the antibacterial mechanism is associated with bacterial membrane interaction. Our study implies that HDP mimicking cyclic peptoid polymers have potential application in treating drug-resistant bacterial infections.

Biomaterials Science

Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria†

Abstract

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Host defense peptide mimicking cyclic peptoid polymers exerting strong activity against drug-resistant bacteria

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