海绵Ianthella basta中Bastadins的结构与活性。RYR1 Ca2+通道的调节剂

IF 2.2 4区医学 Q3 CHEMISTRY, MEDICINAL Bioorganic & Medicinal Chemistry Letters Pub Date : 2025-06-01 Epub Date: 2025-03-03 DOI:10.1016/j.bmcl.2025.130165

Melanie A. Franklin , Mariam N. Salib , Juliette Gafni , Isaac N. Pessah , Tadeusz F. Molinski

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引用次数: 0

摘要

RYR1 Ca2+通道介导骨骼肌兴奋-收缩的基本步骤。Bastadins-5和bastadins -6是由酪氨酸和酪胺组装而成的高溴化大双内酰胺，被鉴定为RYR1通道激活的有效增敏剂。在这里，我们提出了一项结构-活性关系的研究，广泛的一组bastadins，和相关的类似物，并定义了稳定RYR1复合物的开放或封闭构象的最低要求。

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Structure-activity of Bastadins from the marine sponge Ianthella basta. Modulators of the RYR1 Ca2+ channel

The RYR1 Ca²⁺ channel mediates essential steps of excitation-contraction in skeletal muscle. Bastadins-5 and -6, highly brominated macrodilactams assembled from tyrosine and tyramine by the marine sponge Ianthella basta, were identified as potent sensitizers of RYR1 channel activation. Here, we present a structure-activity relationships study of a wide panel of bastadins, and related analogs, and define the minimum requirements for stabilizing the RYR1 complex open or closed conformations.

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来源期刊

Bioorganic & Medicinal Chemistry Letters 医学-医药化学

CiteScore

5.70

自引率

3.70%

发文量

463

审稿时长

27 days

期刊介绍： Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.