The Structure of Zetekitoxin AB, a Saxitoxin Analog from the Panamanian Golden Frog Atelopus Zeteki: a Potent Sodium-Channel Blocker
The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: A potent sodium-channel blocker Mari Yotsu-Yamashita*†, Yong H. Kim†‡, Samuel C. Dudley, Jr.§¶, Gaurav Choudhary§¶, Arnold Pfahnl§¶, Yasukatsu Oshimaʈ, and John W. Daly** *Graduate School of Agricultural Science, Tohoku University, Sendai 981-8555, Japan; ‡Center for Molecular Design and Synthesis, Department of Chemistry, Korea Advanced Institute of Science and Technology, Taejon 305-701, Korea; §Department of Medicine, Emory University, Atlanta, GA 30322; ¶Atlanta Veterans Affairs Medical Center, Decatur, GA 30033; ʈGraduate School of Life Science, Tohoku University, Sendai 981-8555, Japan; and **Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-0820 Contributed by John W. Daly, January 23, 2004 Bufonid anurans of the genus Atelopus contain both steroidal frogs, collected before restrictions, and spectral analysis showed bufadienolides and various guanidinium alkaloids of the tetrodo- that zetekitoxin AB (Fig. 1, 1) is a saxitoxin analog with an toxin class. The former inhibit sodium-potassium ATPases, whereas unprecedented 1,2-oxazolidine ring-fused lactam moiety. The the latter block voltage-dependent sodium channels. The structure inhibitory effects of zetekitoxin AB on voltage-dependent so- of one guanidinium alkaloid, zetekitoxin AB, has remained a dium channels expressed in Xenopus oocytes indicate that zete- mystery for over 30 years. The structure of this alkaloid now has kitoxin AB is an extremely potent sodium channel blocker, been investigated with a sample of Ϸ0.3 mg, purified from extracts manyfold more potent than saxitoxin, but with a similar profile obtained decades ago from the Panamanian golden frog Atelopus of activity at sodium channel isoforms.
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