PTP1B选择性抑制剂的设计及分子对接研究  

Design selective inhibitors by targeting the protein-tyrosine phosphatase (PTP1B) with glide approach

作　　者：王歆[1] 马英[2] 郁彭[1] 王润玲[2] 

机构地区：[1]天津科技大学生物工程学院,天津300457 [2]天津医科大学药学院,天津300070

出　　处：《天津医科大学学报》2013年第4期287-289,293,共4页Journal of Tianjin Medical University

摘　　要：目的:设计蛋白质酪氨酸酯酶1B(PTP1B)选择性抑制剂。方法:应用Schrodinger Suite2009研究4B3与PTP1B的结合模型,修饰结构,建立小分子库,分子对接,预测小分子ADME(吸收、分布、代谢、排泄)。结果:设计出一系列新的PTP1B选择性抑制剂。分子对接研究表明,新抑制剂与已报道的4B3相比有更好的结合能力,都可与第一活性位点和第二活性位点形成氢键,而原始配体只能与第一活性位点残基形成氢键。通过ADME预测得出设计出的化合物均符合类药5原则。结论:通过计算机辅助设计得到的小分子与PTP1B的结合能力理论上优于抑制剂4B3。Objective： To develop selective inhibitors for targeting the protein-tyrosine phosphatase （FFP1B）. Methods： The binding mode of 4B3 and PTP1B, the optimization of candidates, the small molecular library, molecular docking and the prediction of ADME（absorption, distribution, metabolism, and excretion） of candidates were carried out using Schrodinger Suite2009. Results： A novel class of PTP1B selective inhibitors was discovered. These molecules could form hydrogen bonds with the first and the second active site, while the original complex could only exhibit hydrogen bonds with the first active site. And the values for these novel candidates were all within the reasonable ranges according to ADME prediction. Conclusion： The binding affinity of the designed molecules is theoretically superior to the 4B3 in PTP1B.

关 键 词：蛋白质酪氨酸酯酶1B 选择性抑制剂 药物设计 类药性 

分 类 号：R914.2[医药卫生—药物化学]