Catania A, Grieco P, Randazzo A, Novellino E, Gatti S, Rossi C, Colombo G, Lipton J M
Division of Internal Medicine, Ospedale Maggiore di Milano IRCCS, 20122 Milano, Italy.
J Pept Res. 2005 Jul;66(1):19-26. doi: 10.1111/j.1399-3011.2005.00265.x.
Previous research has shown that the immunomodulatory peptide alpha-melanocyte-stimulating hormone (alpha-MSH) and its carboxy-terminal tripeptide KPV (Lys-Pro-Val alpha-MSH11-13) have antimicrobial influences. By inserting a Cys-Cys linker between two units of KPV, we designed the dimer [Ac-CKPV]2 that showed excellent candidacidal effects in pilot tests and was the subject of further investigations. [Ac-CKPV]2 was active against azole-resistant Candida spp. Therefore, the molecule appeared a promising candidate for therapy of fungal infections and was the subject of a structural study. 1H-NMR and restrained mechanic and dynamic calculations suggest that the peptide adopts an extended backbone structure with a beta-turn-like structure. These results open a pathway to development of additional novel compounds that have candidacidal effects potentially useful against clinical infections.
先前的研究表明，免疫调节肽α-黑素细胞刺激素（α-MSH）及其羧基末端三肽KPV（赖氨酸-脯氨酸-缬氨酸α-MSH11-13）具有抗菌作用。通过在KPV的两个单元之间插入一个半胱氨酸-半胱氨酸连接体，我们设计了二聚体[Ac-CKPV]2，其在初步试验中显示出优异的杀念珠菌效果，并成为进一步研究的对象。[Ac-CKPV]2对唑类耐药念珠菌属具有活性。因此，该分子似乎是治疗真菌感染的一个有前景的候选药物，并成为一项结构研究的对象。1H-NMR以及受限力学和动力学计算表明，该肽采用具有β-转角样结构的伸展主链结构。这些结果为开发具有潜在抗临床感染作用的新型杀念珠菌化合物开辟了一条途径。
