Design of transition‐state analogues for gaba‐transaminase

Peter R Andrews, Magdy Iskander, G P Jones, David Winkler

Research output: Contribution to journalArticleResearchpeer-review

12 Citations (Scopus)

Abstract

Compounds which inhibit the mitochondrial enzyme GABA-transaminase have considerable potential as anticonvulsant drugs. An approach which may provide potent and specific enzyme inhibitors involves the use of the transition-state structure of the reaction catalyzed by the enzyme as a template for the design of transition-state analogues. Molecular orbital calculations have been used to calculate the potential energy surface and identify the transition-state structure for the reaction catalyzed by GABA-transaminase. A series of transition-state analogues based on this structure have been synthesized and were found to be biologically active. An active site model has also been developed on the basis of the calculated reaction pathway.
Original languageEnglish
Pages (from-to)345-353
Number of pages9
JournalInternational Journal of Quantum Chemistry
Volume22
Issue numberS9
DOIs
Publication statusPublished - 1982

Cite this

Andrews, Peter R ; Iskander, Magdy ; Jones, G P ; Winkler, David. / Design of transition‐state analogues for gaba‐transaminase. In: International Journal of Quantum Chemistry. 1982 ; Vol. 22, No. S9. pp. 345-353.
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Design of transition‐state analogues for gaba‐transaminase. / Andrews, Peter R; Iskander, Magdy; Jones, G P; Winkler, David.

In: International Journal of Quantum Chemistry, Vol. 22, No. S9, 1982, p. 345-353.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Design of transition‐state analogues for gaba‐transaminase

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AU - Iskander, Magdy

AU - Jones, G P

AU - Winkler, David

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N2 - Compounds which inhibit the mitochondrial enzyme GABA-transaminase have considerable potential as anticonvulsant drugs. An approach which may provide potent and specific enzyme inhibitors involves the use of the transition-state structure of the reaction catalyzed by the enzyme as a template for the design of transition-state analogues. Molecular orbital calculations have been used to calculate the potential energy surface and identify the transition-state structure for the reaction catalyzed by GABA-transaminase. A series of transition-state analogues based on this structure have been synthesized and were found to be biologically active. An active site model has also been developed on the basis of the calculated reaction pathway.

AB - Compounds which inhibit the mitochondrial enzyme GABA-transaminase have considerable potential as anticonvulsant drugs. An approach which may provide potent and specific enzyme inhibitors involves the use of the transition-state structure of the reaction catalyzed by the enzyme as a template for the design of transition-state analogues. Molecular orbital calculations have been used to calculate the potential energy surface and identify the transition-state structure for the reaction catalyzed by GABA-transaminase. A series of transition-state analogues based on this structure have been synthesized and were found to be biologically active. An active site model has also been developed on the basis of the calculated reaction pathway.

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