Alanine scan-guided synthesis and biological evaluation of analogues of culicinin D, a potent anticancer peptaibol.,Bioorganic & Medicinal Chemistry Letters

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Alanine scan-guided synthesis and biological evaluation of analogues of culicinin D, a potent anticancer peptaibol.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2020-03-23 , DOI: 10.1016/j.bmcl.2020.127135
Iman Kavianinia ₁ , Louise A Stubbing ₁ , Maria R Abbattista ₂ , Paul W R Harris ₃ , Jeff B Smaill ₂ , Adam V Patterson ₂ , Margaret A Brimble ₃

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Culicinin D (1), a 10 amino acid peptaibol originally isolated from Culicinomyces clavisporus, exhibits potent activity against a range of cancer cell lines. Building on our previous work exploring the structure-activity relationship (SAR) of the unusual (2S,4S,6R)-AHMOD residue, a series of analogues of culicinin D were prepared to further investigate the SAR of these peptaibols. Alanine scanning of a potent and readily accessible analogue 23 revealed the effect of each residue on antiproliferative activity, and a small panel of analogues were prepared to explore the SAR of the non-natural amino acid residue (2S,4R)-AMD. Results from the alanine scan were used to design an expanded library of culicinin D analogues, leading to the discovery of cyclohexylalanine analogue 52, which exhibited better antiproliferative activity than the natural product 1.

中文翻译：

丙氨酸扫描导向的合成药物culicin D的类似物（一种有效的抗癌肽）。

Culicinin D（1）是最初从clavisporces clavisporus分离的10个氨基酸的肽醇，对多种癌细胞系均表现出强大的活性。在我们先前探索不寻常的（2S，4S，6R）-AHMOD残基的构效关系（SAR）的基础上，准备了一系列culicinin D的类似物以进一步研究这些肽的SAR。丙氨酸对有效且易于获得的类似物23的扫描揭示了每个残基对抗增殖活性的影响，并准备了一小组类似物以探索非天然氨基酸残基（2S，4R）-AMD的SAR。丙氨酸扫描的结果被用于设计culicinin D类似物的扩展文库，从而发现了环己基丙氨酸类似物52，

更新日期：2020-04-20

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