Gao Yitian, Wu Di, Xi Xinping, Wu Yue, Ma Chengbang, Zhou Mei, Wang Lei, Yang Mu, Chen Tianbao, Shaw Chris
Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, Northern Ireland, UK.
Liaoning Center for Certification of Drug, No.7 Chongshanxi Road, Huanggu District, Shenyang 1110036, China.
Molecules. 2016 Dec 3;21(12):1667. doi: 10.3390/molecules21121667.
Antimicrobial peptides belonging to the phylloseptin family are mainly found in phyllomedusine frogs. These peptides not only possess potent antimicrobial activity but exhibit low toxicity against eukaryotic cells. Therefore, they are considered as promising drug candidates for a number of diseases. In a recent study, potent antimicrobial activity was correlated with the conserved structures and cationic amphiphilic characteristics of members of this peptide family. A phylloseptin peptide precursor was discovered here in the skin secretion of and the mature peptide was validated by MS/MS sequencing, and was subsequently named phylloseptin-PT. The chemically-synthesized and purified phylloseptin-PT displayed activity against and . Nevertheless, a range of cationicity-enhanced peptide analogues of phylloseptin-PT, which contained amino acid substitutions at specific sites, exhibited significant increases in antimicrobial activity compared to native phylloseptin-PT. In addition, alternative conformers which were designed and chemically-synthesized with d-lysine, showed potent antimicrobial activity and enhanced bioavailability. These data indicate that phylloseptins may represent potential candidates for next-generation antibiotics. Thus, rational design through modification of natural antimicrobial peptide templates could provide an accelerated path to overcoming obstacles en-route to their possible clinical applications.
属于叶蛙抗菌肽家族的抗菌肽主要存在于叶泡蛙中。这些肽不仅具有强大的抗菌活性，而且对真核细胞表现出低毒性。因此，它们被认为是治疗多种疾病的有前途的候选药物。在最近的一项研究中，强大的抗菌活性与该肽家族成员的保守结构和阳离子两亲特性相关。在此从[具体物种]的皮肤分泌物中发现了一种叶蛙抗菌肽前体，通过串联质谱测序验证了成熟肽，并随后将其命名为叶蛙抗菌肽 - PT。化学合成并纯化的叶蛙抗菌肽 - PT对[具体菌种1]和[具体菌种2]具有活性。然而，一系列在特定位点含有氨基酸取代的叶蛙抗菌肽 - PT阳离子性增强的肽类似物，与天然叶蛙抗菌肽 - PT相比，抗菌活性显著增加。此外，用D - 赖氨酸设计并化学合成的替代构象体显示出强大的抗菌活性和提高的生物利用度。这些数据表明叶蛙抗菌肽可能代表下一代抗生素的潜在候选物。因此，通过修饰天然抗菌肽模板进行合理设计可以为克服其可能的临床应用途中的障碍提供一条加速途径。
