Design of novel analogues of short antimicrobial peptide anoplin with improved antimicrobial activity.

Abstract

Currently, novel antibiotics are urgently required to combat the emergence of drug-resistant bacteria. Antimicrobial peptides with membrane-lytic mechanism of action have attracted considerable interest. Anoplin, a natural α-helical amphiphilic antimicrobial peptide, is an ideal research template because of its short sequence. In this study, we designed and synthesized a group of analogues of anoplin. Among these analogues, anoplin-4 composed of D-amino acids displayed the highest antimicrobial activity due to increased charge, hydrophobicity and amphiphilicity. Gratifyingly, anoplin-4 showed low toxicity to host cells, indicating high bacterial selectivity. Furthermore, the mortality rate of mice infected with Escherichia coli was significantly reduced by anoplin-4 treatment relative to anoplin. In conclusion, anoplin-4 is a novel anoplin analogue with high antimicrobial activity and enzymatic stability, which may represent a potent agent for the treatment of infection.

• Authors: Yang Wang, Jianbo Chen, Xin Zheng, Xiaoli Yang, Panpan Ma, Ying Cai, Bangzhi Zhang, Yuan Chen
• Journal: Journal of peptide science : an official publication of the European Peptide Society (J Pept Sci) Vol. 20 Issue 12 Pg. 945-51 (Dec 2014) ISSN: 1099-1387 [Electronic] England
• PMID: 25316570 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.

Chemical References

• Anti-Infective Agents
• Antimicrobial Cationic Peptides
• Wasp Venoms
• anoplin

Topics

• Amino Acid Sequence
• Anti-Infective Agents (chemistry, pharmacology)
• Antimicrobial Cationic Peptides (chemistry, pharmacology)
• Cell Membrane Permeability (drug effects)
• Drug Design
• Escherichia coli (drug effects, ultrastructure)
• Microscopy, Electron, Scanning
• Molecular Sequence Data
• Proteolysis
• Wasp Venoms (chemistry, pharmacology)