Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase

D M Williams; D L Jakeman; J S Vyle; M P Williamson; G M Blackburn

doi:10.1016/s0960-894x(98)00466-1

Synthesis and binding of stable bisubstrate ligands for phosphoglycerate kinase

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2603-8. doi: 10.1016/s0960-894x(98)00466-1.

Authors

D M Williams¹, D L Jakeman, J S Vyle, M P Williamson, G M Blackburn

Affiliation

¹ Krebs Institute, Department of Chemistry, University of Sheffield, UK.

PMID: 9873589
DOI: 10.1016/s0960-894x(98)00466-1

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.

MeSH terms

Adenosine Diphosphate / analogs & derivatives*
Adenosine Monophosphate / analogs & derivatives*
Catalysis
Chromatography, High Pressure Liquid
Diphosphoglyceric Acids / chemistry
Diphosphoglyceric Acids / metabolism
Drug Design
Kinetics
Ligands
Magnetic Resonance Spectroscopy
Models, Chemical
Phosphoglycerate Kinase / metabolism*

Substances

Diphosphoglyceric Acids
Ligands
glycerate 1,3-biphosphate
Adenosine Monophosphate
Adenosine Diphosphate
Phosphoglycerate Kinase