TY - JOUR
T1 - 4-(oxoalkyl)-substituted gaba analogues as inactivators and substrates of gaba aminotransferase
AU - Burke, James R.
AU - Silverman, Richard B.
N1 - Funding Information:
The authors are grateful to the National Institutes of Health (Grant NS15703) for financial support of this research.
PY - 1991
Y1 - 1991
N2 - On the basis of the mechanism of inactivation of γaminobutyric acid (GABA) aminotransferase by γethynyl GABA that was reported recently (Burke and Silverman, manuscript submitted), three 4-(oxoalkyl)-substituted GABA analogues, 4-amino-5-oxohexanoic acid (7), 4-amino-5-oxopentanoic acid (8), and 4-amino-6-oxohexanoic acid (9) were synthesized and tested as inactivators. Only 8 was an inactivator of the enzyme. A mechanism for the inactivation by 8 is proposed as well as rationalizations for the lack of inactivation by 7 and 9.
AB - On the basis of the mechanism of inactivation of γaminobutyric acid (GABA) aminotransferase by γethynyl GABA that was reported recently (Burke and Silverman, manuscript submitted), three 4-(oxoalkyl)-substituted GABA analogues, 4-amino-5-oxohexanoic acid (7), 4-amino-5-oxopentanoic acid (8), and 4-amino-6-oxohexanoic acid (9) were synthesized and tested as inactivators. Only 8 was an inactivator of the enzyme. A mechanism for the inactivation by 8 is proposed as well as rationalizations for the lack of inactivation by 7 and 9.
KW - 4-amino-5-oxohexanoic acid
KW - 4-amino-5-oxopentanoic acid
KW - 4-amino-6-oxohexanoic acid
KW - Enzyme inactivation
KW - γAminobutyric acid
KW - γaminobutyric acid aminotransferase
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U2 - 10.3109/14756369109080058
DO - 10.3109/14756369109080058
M3 - Article
C2 - 1669447
AN - SCOPUS:0025851241
SN - 1475-6366
VL - 5
SP - 199
EP - 205
JO - Journal of Enzyme Inhibition and Medicinal Chemistry
JF - Journal of Enzyme Inhibition and Medicinal Chemistry
IS - 3
ER -