title: 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.affiliation: College of Agronomy, Gansu Agricultural University, Lanzhou, 730000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yang
authors.forename: Panpan
authors.initials: P
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Bangzhi
authors.initials: B
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D008969:Molecular Sequence Data; D059748:Proteolysis; D014862:Wasp Venoms / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D014862:Wasp Venoms; C443041:anoplin
keywords: analogue of anoplin; antimicrobial activity; antimicrobial peptide; enzymatic stability