Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
CONFORMATIONAL-ANALYSIS OF THE SODIUM-CHANNEL MODULATOR, BREVETOXIN-A, COMPARISON WITH BREVETOXIN-B CONFORMATIONS, AND A HYPOTHESIS ABOUT THE COMMON PHARMACOPHORE OF THE SITE-5 TOXINS
Autore:
REIN KS; BADEN DG; GAWLEY RE;
Indirizzi:
UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI MIAMI FL 33149 UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI MIAMI FL 33149 UNIV MIAMI,DEPT CHEM CORAL GABLES FL 33124
Titolo Testata:
Journal of organic chemistry
fascicolo: 8, volume: 59, anno: 1994,
pagine: 2101 - 2106
SICI:
0022-3263(1994)59:8<2101:COTSMB>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT-BRAIN SYNAPTOSOMES; PTYCHODISCUS-BREVIS; MOLECULAR MECHANICS; BINDING; RECEPTOR; PHARMACOLOGY; MEMBRANES; SOFTWARE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
27
Recensione:
Indirizzi per estratti:
Citazione:
K.S. Rein et al., "CONFORMATIONAL-ANALYSIS OF THE SODIUM-CHANNEL MODULATOR, BREVETOXIN-A, COMPARISON WITH BREVETOXIN-B CONFORMATIONS, AND A HYPOTHESIS ABOUT THE COMMON PHARMACOPHORE OF THE SITE-5 TOXINS", Journal of organic chemistry, 59(8), 1994, pp. 2101-2106

Abstract

The marine neurotoxins brevetoxin A, brevetoxin B, and ciguatoxin bind to the same site (site 5) on the voltage-gated sodium channel. This work, and the following paper in this issue, describe efforts to identify the common pharmacophore and to develop a ligand-receptor model for the binding of these neurotoxins to site 5. Conformational analysis of brevetoxin A has been completed using ah internal coordinate Monte Carlo search protocol. Within 6 kcal/mol of the global minimum (in vacuo), there are 48 conformations of brevetoxin A. In chloroform or water solvent, the calculated relative energies change, but no new minima appear. Like brevetoxin B, brevetoxin A has both straight and bent conformers available. Elimination of several G-ring crown conformers fromconsideration and comparison of the two brevetoxin backbones indicates that those that match most closely in overall shape and location of functional groups are straight. We postulate that the common pharmacophore is a roughly cigar-shaped molecule (similar to 30 Angstrom long) bound to its receptor primarily by hydrophobic and nonpolar solvation forces, possibly aided by strategically placed,hydrogen bonds near thesite of the lactone carbonyl in the receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 17:45:35