Site-Specific Antagonists to Tetrodotoxin and Saxitoxin

Abstract

Towards the objective of developing site-specific antagonists to tetrodotoxin (TTX) and saxitoxin (STX), work has been progressing in two directions. First, three new TTX analogues (6-epi TTX, 11-deoxyTTX and chiriquitoxin) and two new STX analogues (deoxydecarbamoylSTX and decarbamoylneoSTX) have been studied for their relative potencies in blocking the sodium channel. From these studies, the number of stereospecific similar groups in TTX and sTX have been expanded from 3 to 5. As a result of these efforts, the TTX/STX binding site has been deduced as being a 'cave' of about 8 A wide, 6 A tall, and 4-5 A deep. A second direction of our work is synthesis of site-specific antagonists. Because of the new understanding of the TTX/STX binding site, new chemical directions for synthesis of antagonists are under way. Additionally, a new chemically reactive TTX analogue, 11-oxo TTX, has been made synthetically, which will serve as a most useful intermediary for further derivatization. Keywords: RA 1, Binding sites, Tetrodotoxin, Saxitoxin, Site- specific antagonists, Chemical analysis, Sodium-channel effectors, Guanidinium group, Toxin molecules.

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Document Details

Document Type
Technical Report
Publication Date
May 01, 1990
Accession Number
ADB145447

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  • C. Y. Kao

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  • State University of New York

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  • Biomedical

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