Accession Number : ADA253969


Title :   Site-Specific Antagonists to Tetrodotoxin and Saxitoxin,


Corporate Author : STATE UNIV OF NEW YORK AT BROOKLYN


Personal Author(s) : Kao, C Y


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a253969.pdf


Report Date : 01 May 1992


Pagination or Media Count : 5


Abstract : Through studies on structure-activity relations of some natural and synthetic analogs of TTX and STX, and by complementarity considerations, the binding site for these toxins have been deduced as being a pocket 9.5 A (width) x 6 A (height) x 5 A (depth). There are 7 anchoring site points ( a - g) in the receptor which interact with the toxin molecules. Past attempts in synthesizing agonists and antagonists of the toxins have focussed on compounds which could bind to sites a (ion-pairing site), b and c (hydrogen-bonding sites). These attempts have not been successful. In the past year, we have attempted to synthesize compounds which could bind to sites a, f and g. Twelve compounds were synthesized and 9 tested. They have ED 50's for blocking sodium channel ranging from 0.5 to 10 mM. All of them also interfer with potassium channels to varying degrees. We continued to collect more 11-oxoTTX for synthesizing a specifically labelled 3HTTX and photoactivatable derivatives of TTX. A photo label, 4- amidopentafluronitrobenzene, has been synthesized, and we are coupling it to 11- oxoTTX. Biological effects of this material remain to be tested.


Descriptors :   *TOXICITY , *NERVE CELLS , *TOXICOLOGY , IONS , MOLECULES , STRUCTURES , DEPTH , BONDING , HEIGHT , POTASSIUM , COUPLINGS , LABELS , CHANNELS , BLOCKING , ANALOGS , HYDROGEN , SODIUM , SITES , MATERIALS


Subject Categories : Toxicology


Distribution Statement : APPROVED FOR PUBLIC RELEASE