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Aspartyl Phosphonates and Phosphoramidates: The First Synthetic Inhibitors of Bacterial Aspartate‐Semialdehyde Dehydrogenase
Author(s) -
Cox Russell J.,
Gibson Jennifer S.,
Mayo Martín María Belén
Publication year - 2002
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/1439-7633(20020902)3:9<874::aid-cbic874>3.0.co;2-v
Subject(s) - chemistry , dehydrogenase , biochemistry , enzyme , combinatorial chemistry
The synthesis of methylene phosphonate, difluoromethylene phosphonate and phosphoramidate analogues of aspartyl phosphate, together with reduced analogues, is described. These compounds were shown to be effective inhibitors of aspartate‐semialdehyde dehydrogenase (ASA‐DH) from Escherichia coli. However, despite the structural similarity of the compounds, different patterns of inhibition were observed, indicative of two phases of recognition and binding. Correlation between measured inhibition constants with p K a values supports the theory that binding at the phosphate binding site is optimised for singly ionised phosphate analogues.