Document Detail


Synthesis, conformation and biological evaluation of the enantiomers of 3-fluoro-gamma-aminobutyric acid ((R)- and (S)-3F-GABA): an analogue of the neurotransmitter GABA.
MedLine Citation:
PMID:  17990263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gamma-aminobutyric acid or GABA (1) is one of the major inhibitory amino acid neurotransmitters of the central nervous system. This article describes the first synthesis of both the (R)- and (S)- enantiomers of 3-fluoro-GABA (2, 3F-GABA). DFT calculations were carried out in a continuum solvent model (PCM-B3LYP) to estimate the preferred conformations of 3F-GABA in aqueous solution. NMR coupling constants were calculated for each conformer and were then used to simulate the NMR spectra to evaluate the solution conformation of 3F-GABA. A preliminary evaluation of the 3F-GABA enantiomers shows that they act similarly as agonists of cloned GABA(A) receptors; however, they behave quite differently in a whole animal (Xenopus laevis tadpole model).
Authors:
Gildas Deniau; Alexandra M Z Slawin; Tomas Lebl; Fatima Chorki; Jon P Issberner; Tanja van Mourik; Judith M Heygate; Jeremy J Lambert; Lori-An Etherington; Keith T Sillar; David O'Hagan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chembiochem : a European journal of chemical biology     Volume:  8     ISSN:  1439-7633     ISO Abbreviation:  Chembiochem     Publication Date:  2007 Dec 
Date Detail:
Created Date:  2007-12-19     Completed Date:  2008-02-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100937360     Medline TA:  Chembiochem     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2265-74     Citation Subset:  IM    
Affiliation:
School of Chemistry and Centre for Biomolecular Sciences, University of St. Andrews, St. Andrews, Fife, KY16 9ST, Scotland, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Assay
Drug Evaluation
GABA Agents / chemical synthesis,  chemistry,  pharmacology
Humans
Models, Biological*
Molecular Structure
Stereoisomerism
Xenopus laevis / embryology
gamma-Aminobutyric Acid / analogs & derivatives*,  chemical synthesis,  chemistry,  pharmacology
Grant Support
ID/Acronym/Agency:
//Wellcome Trust
Chemical
Reg. No./Substance:
0/3-fluoro-gamma-aminobutryic acid; 0/GABA Agents; 56-12-2/gamma-Aminobutyric Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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