2. Academic Validation
  3. A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine

A novel antimicrobial peptide with broad-spectrum and exceptional stability derived from the natural peptide Brevicidine

  • Eur J Med Chem. 2024 Apr 5:269:116337. doi: 10.1016/j.ejmech.2024.116337.
Ping Yang 1,  Wenbo Mao 1,  Jingying Zhang 1,  Yinyin Yang 1,  Fangyan Zhang 1,  Xu Ouyang 1,  Beibei Li 1,  Xiaoyan Wu 1,  Zufang Ba 1,  Kaixin Ran 1,  Yali Tian 1,  Hui Liu 2,  Yun Zhang 2,  Sanhu Gou 2,  Chao Zhong 3,  Jingman Ni 4
Affiliations

Affiliations

  • 1 Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China.
  • 2 Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China.
  • 3 Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: zhongc@lzu.edu.cn.
  • 4 Institute of Pharmaceutics, School of Pharmacy, Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, and Research Unit of Peptide Science, Chinese Academy of Medical Sciences, 2019RU066, Lanzhou University, Lanzhou, 730000, PR China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, PR China. Electronic address: nijm@lzu.edu.cn.
PMID: 38537511 DOI: 10.1016/j.ejmech.2024.116337
Abstract

The global issue of Antibiotic resistance is increasingly severe, highlighting the urgent necessity for the development of new Antibiotics. Brevicidine, a natural cyclic Lipopeptide, exhibits remarkable antimicrobial activity against Gram-negative bacteria. In this study, a comprehensive structure-activity relationship of Brevicidine was investigated through 20 newly synthesized cyclic Lipopeptide analogs, resulting in the identification of an optimal linear analog 22. The sequence of analog 22 consisted of five d-amino acids and four non-natural amino acid 2,5-diaminovaleric acid (Orn) and conjugated with decanoic acid at N-terminal. Compared to Brevicidine, analog 22 was easier to synthesize, and exerted broad spectrum antimicrobial activity and excellent stability (t1/2 = 40.98 h). Additionally, analog 22 demonstrated a rapid bactericidal effect by permeating non-specifically through the Bacterial membranes, thereby minimizing the likelihood of inducing resistance. Moreover, it exhibited remarkable efficacy in combating Bacterial biofilms and reversing Bacterial resistance to conventional Antibiotics. Furthermore, it effectively suppressed the growth of bacteria in vital organs of mice infected with S. aureus ATCC 25923. In conclusion, analog 22 may represent a potential antimicrobial peptide for further optimization.

Keywords

Antimicrobial spectrum; Brevicidine; Hydrophobicity; Linearization; Stability.

Figures
Products