Wan Yang, Stanovych Andrii, Gori Didier, Zirah Séverine, Kouklovsky Cyrille, Alezra Valérie
National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China; Faculté des Sciences d'Orsay, Univ. Paris-Sud, Laboratoire de Méthodologie, Synthèse et Molécules Thérapeutiques, ICMMO, UMR 8182, CNRS, Université Paris-Saclay, Bât 410, 91405 Orsay, France.
Faculté des Sciences d'Orsay, Univ. Paris-Sud, Laboratoire de Méthodologie, Synthèse et Molécules Thérapeutiques, ICMMO, UMR 8182, CNRS, Université Paris-Saclay, Bât 410, 91405 Orsay, France.
Eur J Med Chem. 2018 Apr 10;149:122-128. doi: 10.1016/j.ejmech.2018.02.053. Epub 2018 Feb 21.
We describe here the synthesis and biological activity study of a pair of diastereomeric analogues of Gramicidin S using β,γ-diamino acids as β-turn mimic. The synthesis of the orthogonally protected β,γ-diamino acids was achieved in 6 steps starting from d-alanine. The analogues were then synthesized in solution phase and on solid phase. Biological activity tests showed that, compared with Gramicidin S, both analogues exerted diminished hemolytic activity while they retained interesting antibacterial activity.
我们在此描述了使用β,γ-二氨基酸作为β-转角模拟物对短杆菌肽S的一对非对映异构体类似物进行的合成及生物活性研究。从d-丙氨酸开始，通过6步反应实现了正交保护的β,γ-二氨基酸的合成。然后在溶液相和固相中合成了这些类似物。生物活性测试表明，与短杆菌肽S相比，这两种类似物的溶血活性均有所降低，同时保留了有趣的抗菌活性。
