Dong Jizhe, Gong Yanchun, Liu Jun, Chen Xiangfeng, Wen Xiaoan, Sun Hongbin
State Key Laboratory of Natural Medicines and Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, China.
Nanjing Haiguang Applied Chemistry Institute, Jiangsu Aosaikang Pharmaceutical Co. Ltd, Nanjing 211112, China.
Bioorg Med Chem. 2014 Feb 15;22(4):1383-93. doi: 10.1016/j.bmc.2013.12.061. Epub 2014 Jan 7.
All eight stereoisomers of saxagliptin have been synthesized and evaluated for their inhibitory activity against DPP-IV. It was unambiguously confirmed that the configuration of saxagliptin was critical to potent inhibition of DPP-IV. Docking study was performed to elucidate the configuration-activity relationship of saxagliptin stereoisomers. Tyr662 and Tyr470 have been suggested as the key residues of DPP-IV interacting with the inhibitors. This work provides valuable information for further inhibitor design against DPP-IV.
已合成了沙格列汀的所有八种立体异构体，并评估了它们对二肽基肽酶-IV（DPP-IV）的抑制活性。明确证实，沙格列汀的构型对有效抑制DPP-IV至关重要。进行了对接研究以阐明沙格列汀立体异构体的构效关系。已提出Tyr662和Tyr470是DPP-IV与抑制剂相互作用的关键残基。这项工作为进一步设计针对DPP-IV的抑制剂提供了有价值的信息。
Zotero 插件