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ω‐Fluoromethyl Analogues of ω‐Amino Acids as Irreversible Inhibitors of 4‐Aminobutyrate: 2‐ Oxoglutarate Aminotransferase
Author(s) -
Bey P.,
Jung M. J.,
Gerhart F.,
Schirlin D.,
Dorsselaer V.,
Casara P.
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb04688.x
Subject(s) - in vivo , inhibitory postsynaptic potential , chemistry , in vitro , trifluoromethyl , stereochemistry , alanine , enzyme , biochemistry , beta (programming language) , amino acid , alpha (finance) , biology , organic chemistry , alkyl , microbiology and biotechnology , neuroscience , medicine , construct validity , nursing , computer science , patient satisfaction , programming language
Abstract— ω ‐Monofluoromethyl and ω‐difluoromethyl analogues of the known substrates of GABA‐T, β ‐alanine, γ ‐aminobutyric acid, and 5‐aminopentanoic acid, are time dependent inhibitors of purified 4‐aminobutyrate: 2‐oxoglutarate aminotransferase (GABA‐T). The inhibitory activity decreases with increasing chain length. In vitro , inhibitory activity decreases with increasing fluorine substitution of the methyl group. In vivo , β ‐difluoromethyl‐ β ‐alanine and 2,4‐difluoro‐3‐aminobutyric acid are the most potent GABA‐T inhibitors ever reported. Trifluoromethyl derivatives are devoid of GABA‐T inhibitory activity in vitro or in vivo.