Accession Number:

ADB145447

Title:

Site-Specific Antagonists to Tetrodotoxin and Saxitoxin

Descriptive Note:

Annual rept. 1 Apr 1989-31 Mar 1990

Corporate Author:

STATE UNIV OF NEW YORK DOWNSTATE MEDICAL CENTER BROOKLYN

Personal Author(s):

• Kao, C. Y.

Report Date:

1990-05-01

Pagination or Media Count:

10.0

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 TTXSTX 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 TTXSTX 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.

Descriptors:

• *SODIUM
• *CHANNELS
• *TOXINS AND ANTITOXINS
• SYNTHESIS
• CHEMICALS
• MOLECULES
• SITES
• ORIENTATION(DIRECTION)
• BINDERS
• CHEMICAL ANALYSIS
• POTENCY
• PHARMACOLOGICAL ANTAGONISTS

Subject Categories:

• Biochemistry
• Toxicology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE