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Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase
D M Williams1, D L Jakeman, J S Vyle
1Krebs Institute, Department of Chemistry, University of Sheffield, UK.
Bioorganic & Medicinal Chemistry Letters
|January 5, 1999
Abstract:
Stable bisubstrate ligands of phosphoglycerate kinase (PGK) have been synthesized with AMP or ADP conjugated to hydrolytically-stable, symmetrical analogues of 1,3-bisphosphoglycerate and their binding to yeast PGK evaluated. Their Kds decrease with net negative charge, with a penta-anionic analogue 7 showing highest affinity-in accordance with its approximation to the transition state for the reaction catalysed by PGK.