化学
糖原磷酸化酶
立体化学
三萜
变构调节
萜烯
激活剂(遗传学)
结构-活动关系
生物活性
苷元
部分
生物化学
酶
糖苷
受体
体外
医学
替代医学
病理
作者
Xiaoan Wen,Hongbin Sun,Jun Li,Keguang Cheng,Pu Zhang,Liying Zhang,Hao Jia,Luyong Zhang,Pei‐Zhou Ni,S.E. Zographos,D.D. Leonidas,Kyra-Melinda Alexacou,Thanasis Gimisis,Joseph M. Hayes,Nikos G. Oikonomakos
摘要
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.
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