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从叶泡蟾皮肤分泌物中发现的 Phylloseptins,可防御革兰氏阳性菌并抑制非小细胞肺癌细胞系的增殖。

Discovery of Phylloseptins that Defense against Gram-Positive Bacteria and Inhibit the Proliferation of the Non-Small Cell Lung Cancer Cell Line, from the Skin Secretions of Phyllomedusa Frogs.

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China.

Natural Drug Discovery Group, School of Pharmacy, Queen's University, Belfast BT9 7BL, UK.

出版信息

Molecules. 2017 Aug 29;22(9):1428. doi: 10.3390/molecules22091428.

Abstract

The growing occurrence of bacterial resistance to conventional antibiotics has called for the development of new classes of antimicrobial agents. Antimicrobial peptides (AMPs) with broad antimicrobial spectrum derived from frog skin secretions have been demonstrated to be promising candidates for new antibiotic development. A proven rich source of these compounds are the skin secretions of the frogs in the genus. In this study, two novel phylloseptin peptides-phylloseptin-PTa and phylloseptin-PHa-were isolated from the skin secretions of the South American frogs, () and () through parallel transcriptomic and peptidomic studies. Replicates obtained by chemical synthesis were structurally analysed and shown to adopt an α-helix configuration in an amphiphilic environment. Both peptides demonstrated antimicrobial activities against planktonic Gram-positive bacteria strains, including , and methicillin-resistant , biofilms, as well as cytostatic effects on the non-small cell lung cancer cell line, NCI-H157, with relatively low haemolysis on horse erythrocytes and low cytotoxicity on the human microvascular endothelial cell line, HMEC-1. The discovery of phylloseptin peptides may further inspire the development of new types of antibiotics.

摘要

细菌对传统抗生素的耐药性日益增加,这就需要开发新类别的抗菌药物。从青蛙皮肤分泌物中提取的具有广谱抗菌活性的抗菌肽(AMPs)已被证明是开发新型抗生素的有前途的候选物。这些化合物的一个已知丰富来源是属的青蛙的皮肤分泌物。在这项研究中,通过平行转录组学和肽组学研究,从南美青蛙()和()的皮肤分泌物中分离出两种新型 Phylloseptin 肽——Phylloseptin-PTa 和 Phylloseptin-PHa。通过化学合成获得的重复序列进行了结构分析,并显示在亲脂环境中采用 α-螺旋构象。这两种肽都表现出对浮游革兰氏阳性细菌菌株的抗菌活性,包括 、 和耐甲氧西林的 ,生物膜,以及对非小细胞肺癌细胞系 NCI-H157 的细胞生长抑制作用,对马红细胞的溶血作用相对较低,对人微血管内皮细胞系 HMEC-1 的细胞毒性较低。Phylloseptin 肽的发现可能会进一步激发新型抗生素的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/338e/6151776/e1e8dce8599c/molecules-22-01428-g001.jpg

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