TY - JOUR
T1 - Transition-state analogues as inhibitors for GABA-aminotransferase
AU - Iskander, Magdy
AU - Andrews, PR
AU - Winkler, David
AU - Brinkworth, RI
AU - Di Paola, C.
AU - Cavell, S.
AU - Issa, J.
PY - 1991
Y1 - 1991
N2 - Our previous calculations on the reaction catalysed by GABA-aminotransferase (GABA-T) have been utilized in this work in order to synthesize a series of reversible inhibitors of this enzyme. The synthesized transition-state analogues and their precursors inhibited GABA-T competitively in both the holoenzyme and apoenzyme at 10-3 and 10-5 M, respectively. In the case of the holoenzyme, the transition-state analogue series (the conformationally restricted series) gave a significant increase in inhibition values over the open (less conformationally restricted) series.
AB - Our previous calculations on the reaction catalysed by GABA-aminotransferase (GABA-T) have been utilized in this work in order to synthesize a series of reversible inhibitors of this enzyme. The synthesized transition-state analogues and their precursors inhibited GABA-T competitively in both the holoenzyme and apoenzyme at 10-3 and 10-5 M, respectively. In the case of the holoenzyme, the transition-state analogue series (the conformationally restricted series) gave a significant increase in inhibition values over the open (less conformationally restricted) series.
KW - biochemical evaluation
KW - enzyme inhibitors
KW - GABA-aminotransferase
KW - transition-state analogues
UR - http://www.scopus.com/inward/record.url?scp=0025807805&partnerID=8YFLogxK
U2 - 10.1016/0223-5234(91)90022-F
DO - 10.1016/0223-5234(91)90022-F
M3 - Article
VL - 26
SP - 129
EP - 135
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
IS - 2
ER -