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

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(Naeg0.7Npfbg0.3)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.

• Authors: 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
• Journal: Biomaterials science (Biomater Sci) Vol. 10 Issue 16 Pg. 4515-4524 (Aug 09 2022) ISSN: 2047-4849 [Electronic] England
• PMID: 35788576 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• Peptoids
• Polymers

Topics

• Anti-Bacterial Agents (chemistry, pharmacology)
• Antimicrobial Cationic Peptides
• Bacteria
• Microbial Sensitivity Tests
• Peptoids (chemistry, pharmacology)
• Polymers (chemistry, pharmacology)