High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs

International Journal of Molecular Sciences

Zi Wang¹  Inam Muhammad²  Yiming Wang²  Hongxia Ma²  Lingcong Kong²  Xiuyun Jiang²  Boyan Jia²  Ying Zhang²  Zhihua Pei²  Xue Wang² 

[1] College of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao 028000, China;College of Animal Science and Technology, Jilin Agricultural University, Xincheng Street No.2888, Changchun 130118, China;

关键词: antimicrobial peptides;    cell selectivity;    stability;    mechanism;    endotoxin neutralization;   

DOI  :  10.3390/ijms21031140

来源: DOAJ

【 摘 要 】

Antimicrobial peptides (AMPs) have a unique action mechanism that can help to solve global problems in antibiotic resistance. However, their low therapeutic index and poor stability seriously hamper their development as therapeutic agents. In order to overcome these problems, we designed peptides based on the sequence template XXRXXRRzzRRXXRXX-NH₂, where X represents a hydrophobic amino acid like Phe (F), Ile (I), and Leu (L), while zz represents Gly−Gly (GG) or d-Pro−Gly (pG). Showing effective antimicrobial activity against Gram-negative bacteria and low toxicity, designed peptides had a tendency to form an α-helical structure in membrane-mimetic environments. Among them, peptide LR_pG (X: L, zz: pG) showed the highest geometric mean average treatment index (GM_TI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LR_pG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LR_pG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LR_pG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.

【 授权许可】

Unknown