Three-dimensional structure of the α-MSH-derived candidacidal peptide [Ac-CKPV]2
Three-dimensional structure of the α-MSH-derived candidacidal peptide [Ac-CKPV]2
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DOI：
10.1111/j.1399-3011.2005.00265.x
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发表时间：
2005-07-01
期刊：
影响因子：
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通讯作者：
Lipton, JM
中科院分区：
文献类型：
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作者：
Catania, A;Grieco, P;Lipton, JM
先前的研究表明，免疫调节肽α-黑素细胞刺激激素（α-MSH）及其羧基末端三肽KPV（Lys-Pro-Val α-MSH11-13）具有抗菌作用。通过在 KPV 的两个单元之间插入 Cys-Cys 连接子，我们设计了二聚体 [Ac-CKPV](2)，该二聚体在先导测试中显示出优异的候选作用，并成为进一步研究的主题。 [Ac-CKPV](2) 对唑类抗性念珠菌属具有活性。因此，该分子似乎是治疗真菌感染的有希望的候选者，并且是结构研究的主题。 H-1-NMR以及受限的力学和动力学计算表明该肽采用具有β-转角结构的延伸主链结构。这些结果开辟了开发其他具有念珠菌作用的新型化合物的途径，这些化合物可能有助于对抗临床感染。
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. H-1-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.