dc.creator | Kantsadi, A. L. | en |
dc.creator | Manta, S. | en |
dc.creator | Psarra, A. M. G. | en |
dc.creator | Dimopoulou, A. | en |
dc.creator | Kiritsis, C. | en |
dc.creator | Parmenopoulou, V. | en |
dc.creator | Skamnaki, V. T. | en |
dc.creator | Zoumpoulakis, P. | en |
dc.creator | Zographos, S. E. | en |
dc.creator | Leonidas, D. D. | en |
dc.creator | Komiotis, D. | en |
dc.date.accessioned | 2015-11-23T10:32:36Z | |
dc.date.available | 2015-11-23T10:32:36Z | |
dc.date.issued | 2012 | |
dc.identifier | 10.1016/j.ejmech.2012.06.029 | |
dc.identifier.issn | 0223-5234 | |
dc.identifier.uri | http://hdl.handle.net/11615/28885 | |
dc.description.abstract | C5-alkynyl and allcylfurano[2,3-d]pyrimidine glucopyranonucleosides have been synthesized and studied as inhibitors of glycogen phosphorylase b (GPb). Kinetic experiments have shown that most of these compounds were low micromolar inhibitors of the enzyme. The best inhibitor was 1-(beta-D-glucopyranosyl)-5-ethynyluracil (K-i = 4.7 mu M). Crystallographic analysis of these compounds in complex with GPb revealed that inhibitors with a long C5-alkynyl group exploited interactions with beta-pocket of the active site and induced significant conformational changes of the 280s loop compared to GPb in complex with compounds with a short C5-alkynyl group. The results highlight the importance in the length of the aliphatic groups used to enhance inhibitory potency for the exploitation of the hydrophobic beta-pocket. The best of the inhibitors had also a moderate effect on glycogenolysis in the cellular lever with an IC50 value of 291.4 mu M. (C) 2012 Elsevier Masson SAS. All rights reserved. | en |
dc.source | European Journal of Medicinal Chemistry | en |
dc.source.uri | <Go to ISI>://WOS:000307920600076 | |
dc.subject | Pyrimidine gluconucleosides | en |
dc.subject | Glycogen metabolism | en |
dc.subject | Diabetes type 2 | en |
dc.subject | Inhibitor | en |
dc.subject | Glycogen phosphorylase | en |
dc.subject | X-ray crystallography | en |
dc.subject | HEPATIC GLUCOSE-PRODUCTION | en |
dc.subject | PHARMACOLOGICAL INHIBITION | en |
dc.subject | HALOGEN ATOMS | en |
dc.subject | DESIGN | en |
dc.subject | TARGETS | en |
dc.subject | CRYSTALLOGRAPHY | en |
dc.subject | NUCLEOSIDES | en |
dc.subject | COMPUTATION | en |
dc.subject | DERIVATIVES | en |
dc.subject | TOOL | en |
dc.subject | Chemistry, Medicinal | en |
dc.title | The binding of C5-alkynyl and alkylfurano 2,3-d pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment | en |
dc.type | journalArticle | en |