| Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase. | |
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MedLine Citation:
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PMID: 17988865 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The design, synthesis, and evaluation of novel gamma-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. |
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Authors:
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Michael D Clift; Richard B Silverman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-10-22 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry letters Volume: 18 ISSN: 1464-3405 ISO Abbreviation: Bioorg. Med. Chem. Lett. Publication Date: 2008 May |
Date Detail:
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Created Date: 2008-05-21 Completed Date: 2008-10-03 Revised Date: 2010-09-20 |
Medline Journal Info:
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Nlm Unique ID: 9107377 Medline TA: Bioorg Med Chem Lett Country: England |
Other Details:
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Languages: eng Pagination: 3122-5 Citation Subset: IM |
Affiliation:
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Department of Chemistry, Northwestern University, Evanston, IL 60208-3113, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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4-Aminobutyrate Transaminase
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antagonists & inhibitors*,
chemistry Binding, Competitive Computer Simulation Drug Design* Enzyme Inhibitors / chemical synthesis, chemistry, pharmacology Hydrocarbons, Aromatic / chemical synthesis*, chemistry, pharmacology Molecular Structure |
| Grant Support | |
ID/Acronym/Agency:
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GM66132/GM/NIGMS NIH HHS; R01 GM066132-01A2/GM/NIGMS NIH HHS; R01 GM066132-02/GM/NIGMS NIH HHS; R01 GM066132-03/GM/NIGMS NIH HHS; R01 GM066132-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Hydrocarbons, Aromatic; EC 2.6.1.19/4-Aminobutyrate Transaminase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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