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Autor: He, Li, Zhi Zhang, Yun, Tanoh, Marcelle, Chen, Guo-Rong, Praly, Jean-Pierre, Chrysina, Evangelia D., Tiraidis, Costas, Kosmopoulou, Magda, Leonidas, Demetres D., Oikonomakos, Nikos G.
Zdroj: European Journal of Organic Chemistry; February 2007, Vol. 2007 Issue: 4 p596-606, 11p
Abstrakt: Penta-O-acetyl-β-D-glycopyranoses and 1,4-dimethoxybenzene led selectively by electrophilic substitution to C-β-D-glycopyranosyl-1,4-dimethoxybenzenes which were converted by simple and efficient reactions (oxidation, reduction and deacetylation) to the corresponding C-glycosylhydro- and C-glycosylbenzoquinones, with either an acetylated or deprotected sugar moiety. C-β-D-Glucosylbenzoquinone 19 and C-β-D-Glucosylhydroquinone 23 were found to be competitive inhibitors of rabbit muscle glycogen phosphorylase b (GPb), with respect to the substrate α-D-glucose-1-phosphate, with Ki values of 1.3 and 0.9 mM, respectively, whereas C-β-D-glucosylhydroquinone 17 was not effective up to a concentration of 8 mM. In order to elucidate the structural basis of inhibition, we determined the crystal structures of 19 and 23 in complex with GPb at a 2.03–2.05 Å resolution. The complex structures reveal that the inhibitors can be accommodated at the catalytic site at approximately the same position as α-D-glucose and stabilise the transition state conformation of the 280s loop by making several favourable contacts to Asp283 and Asn284 of this loop. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Databáze: Supplemental Index
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