4-(Oxoalkyl)-substituted GABA analogues as inactivators and substrates of GABA aminotransferase.

On the basis of the mechanism of inactivation of gamma-aminobutyric acid (GABA) aminotransferase by gamma-ethynyl 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.