Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5225381 | Tetrahedron | 2007 | 6 Pages |
Kinetic isotope effects provide a powerful method to investigate the mechanisms of enzyme-catalyzed reactions, but often other slow steps in the reaction such as substrate binding or product release suppress the isotopically sensitive step. For reactions at methyl groups, this limitation may be overcomed by measuring the isotope effect by an intra-molecular competition experiment. This requires the synthesis of substrates containing regio-specifically mono- or di-deuterated methyl groups. To facilitate the mechanistic investigations of the adenosylcobalamin-dependent enzyme, glutamate mutase, we have developed a synthesis of mono- and di-deuterated (2S,3S)-3-methylaspartic acids. Key intermediates are the correspondingly labeled mesaconic acids and their dimethyl esters that potentially provide starting materials for a variety of isotopically labeled molecules.
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