3′-Axial CH2OH Substitution on Glucopyranose does not Increase Glycogen Phosphorylase Inhibitory Potency. QM/MM-PBSA Calculations Suggest Why (pages 663–673)
Stella Manta, Andromachi Xipnitou, Christos Kiritsis, Anastassia L. Kantsadi, Joseph M. Hayes, Vicky T. Skamnaki, Christos Lamprakis, Maria Kontou, Panagiotis Zoumpoulakis, Spyridon E. Zographos, Demetres D. Leonidas and Dimitri Komiotis
Version of Record online: 7 MAR 2012 | DOI: 10.1111/j.1747-0285.2012.01349.x
1-[3′-C-(hydroxymethyl)-β-d-glucopyranosyl)]5-fluorouracil has been synthesized and has been identified as an inhibitor of muscle glycogen phosphorylase b. The parent ligand 1-(β-d-glucopyranosyl)5-fluorouracil is 2.9 times more potent. Modeling calculations and X-ray structural studies were performed to identify the source of the greater binding affinity compared to its 3′-substituted glucose derivative.