Abstract
The design, synthesis, and evaluation of novel γ-aminobutyric acid aminotransferase (GABA-AT) inhibitors and inactivators can lead to the discovery of new GABA-related therapeutics. To this end, a series of aromatic amino acid compounds was synthesized to aid in the design of new inhibitors and inactivators of GABA-AT. All compounds were tested as competitive inhibitors of GABA-AT. The amino acids with benzylic amines were also tested as substrates for GABA-AT. It was found that these compounds were all poor competitive inhibitors of GABA-AT, but some were substrates of the enzyme, suggesting their utility as scaffolds for potential GABA-AT mechanism-based inactivators. Computer modeling was used to rationalize the substrate activity of the various compounds.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3122-3125 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 18 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2008 |
Funding
The authors are grateful to the National Institutes of Health (GM66132) for financial support of this research. We thank Dr. Haitao Ji for carrying out the computer modeling and Dr. Graham Lawton and Dr. Wenxin Gu for helpful discussions.
Keywords
- Aromatic amino acid
- Computer modeling
- GABA-AT
- Inhibitor
- Substrate of GABA-AT
- γ-Aminobutyric acid
- γ-Aminobutyric acid aminotransferase
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Molecular Biology
- Biochemistry
- Clinical Biochemistry
- Pharmaceutical Science
- Organic Chemistry