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

• DOI: 10.3390/ijms21031140
• Publication Date: 2020-02-10T16:48:51Z
• Authors: Boyan Jia; Yiming Wang; Ying Zhang; Zi Wang; Xue Wang; Inam Muhammad; Lingcong Kong; Zhihua Pei; Hongxia Ma; Xiuyun Jiang
• Keywords: 0301 basic medicine; endotoxin neutralization; Bacteria; Circular Dichroism; mechanism; Microbial Sensitivity Tests; stability; Article; 3. Good health; antimicrobial peptides; cell selectivity; 03 medical and health sciences; Gram-Negative Bacteria; Microscopy, Electron, Scanning; Antimicrobial Cationic Peptides

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 LRpG (X: L, zz: pG) showed the highest geometric mean average treatment index (GMTI = 73.1), better salt, temperature and pH stability, and an additive effect with conventional antibiotics. Peptide LRpG played the role of anti-Gram-negative bacteria through destroying the cell membrane. In addition, peptide LRpG also exhibited an anti-inflammatory activity by effectively neutralizing endotoxin. Briefly, peptide LRpG has the potential to serve as a therapeutic agent to reduce antibiotic resistance owing to its high therapeutic index and great stability.