High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on D-Pro-Gly Pairs
High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on D-Pro-Gly Pairs
复制标题
以d-Pro-Gly对为中心的对称肽的高细胞选择性及其杀菌机制
DOI：
10.3390/ijms21031140
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发表时间：
2020-02-01
影响因子：
5.6
通讯作者：
Jiang, Xiuyun
中科院分区：
文献类型：
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作者：
Jia, Boyan;Wang, Yiming;Jiang, Xiuyun
抗菌肽（Antimicrobial Peptides，AMP）具有独特的作用机制，有助于解决全球性的抗生素耐药性问题。然而，其治疗指数低和稳定性差严重阻碍了其作为治疗剂的发展。为了克服这些问题，我们基于序列模板XXRXXRRzzRRXXRXX-NH2设计肽，其中X代表疏水性氨基酸，如Phe（F）、Ile（I）和Leu（L），而zz代表Gly-Gly（GG）或d-Pro-Gly（pG）。所设计的多肽对革兰氏阴性菌具有有效的抗菌活性，且毒性较低，在拟膜环境中有形成α-螺旋结构的趋势。其中，肽LRpG（X：L，zz：pG）显示最高的几何平均平均处理指数（GMTI = 73.1），更好的盐、温度和pH稳定性，以及与常规抗生素的加和效应。肽LRpG通过破坏细胞膜发挥抗革兰氏阴性菌的作用。此外，肽LRpG还通过有效中和内毒素而表现出抗炎活性。简言之，肽LRpG由于其高治疗指数和高稳定性而具有用作治疗剂以减少抗生素抗性的潜力。
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.