Wang Youde, Li Shuai, Yan Zhiwei, Guo Yachun, Zhang Liying
Key Laboratory of Traditional Chinese Medicine Research & Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde, 067000, China.
Department of Pathogen Biology, Chengde Medical University, Chengde, Hebei, 067000, China.
Future Med Chem. 2023 Jun;15(11):913-922. doi: 10.4155/fmc-2023-0084. Epub 2023 Jul 3.
Glycogen phosphorylase (GP) is a potential drug target. As the three subtypes of GP are highly conserved, it is difficult to research their specificity. However, compound inhibits the GP subtypes differently and was studied to aid in designing specific inhibitors. Molecular docking showed that the ligands in GP subtype complexes had some differences in spatial conformation and binding modes, stabilized by polar and nonpolar interactions. The results were confirmed through kinetic experiments, with affinities of -85.230 (brain GP), -73.809 (liver GP) and -66.061 kJ/mol (muscle GP). The study provides insight into the possible reasons for differences in compound 's inhibitory activity against the GP subtypes and offers guidance in designing target molecules for regulating selectivity among the subtypes.
糖原磷酸化酶（GP）是一个潜在的药物靶点。由于GP的三种亚型高度保守，很难研究它们的特异性。然而，化合物对GP亚型的抑制作用不同，因此对其进行了研究以辅助设计特异性抑制剂。分子对接表明，GP亚型复合物中的配体在空间构象和结合模式上存在一些差异，这些差异通过极性和非极性相互作用得以稳定。通过动力学实验证实了结果，其亲和力分别为-85.230（脑GP）、-73.809（肝GP）和-66.061 kJ/mol（肌肉GP）。该研究深入探讨了化合物对GP亚型抑制活性存在差异的可能原因，并为设计调节亚型间选择性的靶分子提供了指导。
