Wen, Xiaoan, Sun, Hongbin, Liu, Jun, Cheng, Keguang, Zhang, Pu, Zhang, Liying, Hao, Jia, Zhang, Luyong, Ni, Peizhou, Zographos, Spyros E., Leonidas, Demetres D., Alexacou, Kyra-Melinda, Gimisis, Thanasis, Hayes, Joseph and Oikonomakos, Nikos G. (2008) Naturally Occurring Pentacyclic Triterpenes as Inhibitors of Glycogen Phosphorylase: Synthesis, Structure−Activity Relationships, and X-ray Crystallographic Studies†. Journal of Medicinal Chemistry, 51 (12). pp. 3540-3554. ISSN 0022-2623
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Official URL: http://dx.doi.org/10.1021/jm8000949
Twenty-five naturally occurring pentacyclic triterpenes, 15 of which were synthesized in this study, were biologically evaluated as inhibitors of rabbit muscle glycogen phosphorylase a (GPa). From SAR studies, the presence of a sugar moiety in triterpene saponins resulted in a markedly decreased activity (7, 18−20) or no activity (21, 22). These saponins, however, might find their value as potential natural prodrugs which are much more water-soluble than their corresponding aglycones. To elucidate the mechanism of GP inhibition, we have determined the crystal structures of the GPb−asiatic acid and GPb−maslinic acid complexes. The X-ray analysis indicates that the inhibitors bind at the allosteric activator site, where the physiological activator AMP binds. Pentacyclic triterpenes represent a promising class of multiple-target antidiabetic agents that exert hypoglycemic effects, at least in part, through GP inhibition.
|Schools:||Faculty of Science and Technology > School of Forensic and Applied Sciences|
|Deposited By:||Carmit Erez|
|Deposited On:||08 Apr 2013 12:37|
|Last Modified:||15 Mar 2017 10:44|
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