Abstract
A structural similarity of several monobactams (2-4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7-aminodesacetoxycephalosporanic acids (9, 10) to γaminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These βlactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 125-129 |
| Number of pages | 5 |
| Journal | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Volume | 6 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1992 |
Funding
This work was supported by the National Institutes of Health (NS 15703) to R.B.S. and by an American Cancer Society postdoctoral fellowship to M.H.H. We are grateful to Professor Craig Townsend (Johns Hopkins University) for a gift of 3-aminonocardicinica cid, to Dr. Christopher Cimarusti of the Bristol-Myers Squibb Company for a gift of SQ, 26,771 (4), SQ 27,129 (3). and SQ 30 30,384 (2), and to Dr. Gregory Banik (Abbott Laboratories) for a gift of A-44177 (10).
Keywords
- Cephalosporins
- Monobactams
- Penicillins
- βLactams
- γaminobutyric acid
- γaminobutyric acid aminotransferase
ASJC Scopus subject areas
- Drug Discovery
- Pharmacology