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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: A potent sodium-channel blocker
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The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: A potent sodium-channel blocker

机译：Zetekitoxin AB（一种来自巴拿马金蛙Atelopus zeteki的毒素）类似物的结构：一种有效的钠通道阻滞剂

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摘要

Bufonid anurans of the genus Atelopus contain both steroidal bufadienolides and various guanidinium alkaloids of the tetrodotoxin class. The former inhibit sodium-potassium ATPases, whereas the latter block voltage-dependent sodium channels. The structure of one guanidinium alkaloid, zetekitoxin AB, has remained a mystery for over 30 years. The structure of this alkaloid now has been investigated with a sample of approximate to0.3 mg, purified from extracts obtained decades ago from the Panamanian golden frog Atelopus zeteki. Detailed NMR and mass spectral analyses have provided the structure and relative stereochemistry of zetekitoxin AB and have revealed that it is an analog of saxitoxin. The proposed structure is characterized by richness of heteroatoms (C16H25N8O12S) and contains a unique 1,2-oxazolidine ring-fused lactam, a sulfate ester, and an N-hydroxycarbamate moiety. Zetekitoxin AB proved to be an extremely potent blocker of voltage-dependent sodium channels expressed in Xenopus oocytes. The IC50 values were 280 pM for human heart channels, 6.1 pM for rat brain IIa channels, and 65 pM for rat skeletal muscle channels, thus being roughly 580-, 160-, and 63-fold more potent at these channels than saxitoxin. [References: 37]
机译：Atelopus属的Bufonid anurans既含有甾体类丁二烯内酯，又含有河豚毒素类的各种胍类生物碱。前者抑制钠钾ATP酶，而后者阻断电压依赖性钠通道。一种胍基生物碱zetekitoxin AB的结构在过去三十多年中一直是个谜。现在已经用大约0.3毫克的样品对这种生物碱的结构进行了研究，该样品是从几十年前从巴拿马金蛙Atelopus zeteki提取的提取物中纯化得到的。详细的NMR和质谱分析提供了Zetekitoxin AB的结构和相对立体化学，并揭示了它是saxitoxin的类似物。拟议的结构的特点是杂原子丰富（C16H25N8O12S），并包含独特的1,2-恶唑烷环稠合内酰胺，硫酸酯和N-羟基氨基甲酸酯部分。 Zetekitoxin AB被证明是非洲爪蟾卵母细胞中表达的电压依赖性钠通道的极强阻断剂。人心脏通道的IC50值为280 pM，大鼠脑IIa通道的IC50值为65 pM，大鼠骨骼肌通道的IC50值为65 pM，因此在这些通道上的效力大约比saxitoxin高580、160和63倍。 [参考：37]

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