Jung Hyun Jun, Park Yoonkyung, Sung Woo Sang, Suh Bo Kyoung, Lee Juneyoung, Hahm Kyung-Soo, Lee Dong Gun
Department of Microbiology, College of Natural Sciences, Kyungpook National University, 1370 Sankyuk-dong, Puk-ku, Daegu 702-701, Republic of Korea.
Biochim Biophys Acta. 2007 Jun;1768(6):1400-5. doi: 10.1016/j.bbamem.2007.02.024. Epub 2007 Mar 15.
Pleurocidin (Ple) is a 25-residue peptide which is derived from the skin mucous secretion of the winter flounder (Pleuronectes americanus). In this study, we investigated antifungal effects and its mode of action of Ple on human pathogenic fungi. Ple showed potent antifungal activity with low hemolytic activity. To investigate the antifungal mechanisms of Ple, the cellular localization and membrane interaction of Ple were examined. Protoplast regeneration and membrane-disrupting activity by DPH-labeled membrane support the idea, that Ple exerts fungicidal activity against the human pathogenic fungus Candida albicans with the disruption of a plasma membrane. To aim for which was the application of a therapeutic agent, we designed a synthetic enantiomeric peptide composed of all-d-amino acids to enhance proteolytic resistance. The synthetic all-d-Ple also displayed two-fold more potent antifungal activity than that of all-l-Ple, and its antifungal activity showed proteolytic resistance against various proteases. Therefore, these results suggest a therapeutic potential of all-d-Ple with regard to its proteolytic resistance against human fungal infections.
杀鲆肽（Ple）是一种由25个氨基酸残基组成的肽，它源自美洲拟鲽（Pleuronectes americanus）的皮肤黏液分泌物。在本研究中，我们研究了Ple对人类致病真菌的抗真菌作用及其作用方式。Ple表现出强大的抗真菌活性且溶血活性较低。为了研究Ple的抗真菌机制，我们检测了Ple的细胞定位和膜相互作用。原生质体再生以及由DPH标记膜的膜破坏活性支持了这样一种观点，即Ple通过破坏质膜对人类致病真菌白色念珠菌发挥杀菌活性。为了实现治疗剂的应用目标，我们设计了一种由全d-氨基酸组成的合成对映体肽以增强蛋白水解抗性。合成的全d-Ple也显示出比全l-Ple强两倍的抗真菌活性，并且其抗真菌活性对各种蛋白酶表现出蛋白水解抗性。因此，这些结果表明全d-Ple在抗人类真菌感染的蛋白水解抗性方面具有治疗潜力。
