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评估一种新型抗菌和抗癌肽 Dermaseptin-PS4(Der-PS4)的生物活性,该肽来自 的皮肤分泌物。

Evaluating the Bioactivity of a Novel Antimicrobial and Anticancer Peptide, Dermaseptin-PS4(Der-PS4), from the Skin Secretion of .

机构信息

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

Department of Nutrition, Henry Fok School of Food Science and Engineering, Shaoguan University, Shaoguan 512005, China.

出版信息

Molecules. 2019 Aug 16;24(16):2974. doi: 10.3390/molecules24162974.

Abstract

Dermaseptins belonging to a large family of cationic membrane-disruption antimicrobial peptides display extensive antibacterial and antiproliferative activities depending on a coil-to-helix transition and the specific structural parameters. Herein, a novel dermaseptin peptide named Der-PS4 was discovered from the skin secretion of the waxy monkey tree frog, . The complementary DNA (cDNA)-encoding precursor was obtained relying on "shotgun" cloning, and afterwards, a mature peptide amino acid sequence was identified by reverse-phase high performance liquid chromatography (RP-HPLC) and MS/MS. Specimens were chemically synthesized and applied for further functional studies. Structural analysis demonstrated a higher α-helical content in the membrane-mimetic environment compared with that in the ammonium acetate/water circumstance. Der-PS4 displayed a broad spectrum of antimicrobial activities against tested pathogenic microorganisms, however, exhibiting slight membrane-damaging effectiveness towards horse red blood cells. Coincident with the inhibitory activities on pathogens, Der-PS4 also showed considerable biofilm eradicating impact. Also, Der-PS4 penetrated cell membrane in a relative short period under each minimum bactericidal concentration. In addition, Der-PS4 possessed antiproliferative capacity against five cancer cell lines, while presenting slight suppressing effect on human microvascular endothelial, HMEC-1. These findings provide a promising insight for the discovery and development of novel drugs from a natural source.

摘要

属于阳离子膜破坏抗菌肽大家族的 Dermaseptins 根据螺旋到螺旋的转变和特定的结构参数显示出广泛的抗菌和抗增殖活性。本文从蜡猴树蛙的皮肤分泌物中发现了一种新型的 Dermaseptin 肽,名为 Der-PS4。依赖于“鸟枪法”克隆获得编码前体的互补 DNA(cDNA),然后通过反相高效液相色谱(RP-HPLC)和 MS/MS 鉴定出成熟肽的氨基酸序列。通过化学合成获得样品,并应用于进一步的功能研究。结构分析表明,在模拟膜的环境中,α-螺旋含量高于在乙酸铵/水溶液中的含量。Der-PS4 对测试的致病性微生物表现出广谱的抗菌活性,但对马红细胞的膜损伤作用较弱。与对病原体的抑制活性一致,Der-PS4 对生物膜也有显著的清除作用。此外,在每个最低杀菌浓度下,Der-PS4 都能在相对较短的时间内穿透细胞膜。此外,Der-PS4 对五种癌细胞系具有抗增殖能力,而对人微血管内皮细胞 HMEC-1 则表现出轻微的抑制作用。这些发现为从天然来源发现和开发新型药物提供了有希望的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c966/6719146/c19365f3f0ec/molecules-24-02974-g001.jpg

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