化学工程与技术—DPP-Ⅳ抑制剂三维药效团模型构建.pdfVIP

Hans Journal of Chemical Engineering and Technology 化学工程与技术, 2012, 2, 53-60 doi:10.4236/hjcet.2012.22010 Published Online April 2012 (/journal/hjcet) * 3D Pharmacophore Model Construction of DPP-Ⅳ Inhibitors 1 1# 2 1 1 2 Tianjiao Han , Yueqing Li , Junfeng Gu , Zhi Cao , Weijie Zhao , Xicheng Wang 1School of Pharmaceutical Science and Technology, Dalian University of Technology, Dalian 2State Key Laboratory of Structure Analyses for Industrial Equipment, Dalian University of Technology, Dalian Email: #yueqingli@ Received: Jan. 4th, 2012; revised: Mar. 5th, 2012; accepted: Mar. 12th, 2012 Abstract: The 3D pharmacophore model of DPP-Ⅳ inhibitors was established using the Discovery Studio software with the training set of 20 DPP-Ⅳ inhibitors. The best pharmacophore hypothesis (Hypo 1) consists of one hydro- gen-bond acceptor, one hydrophobic point, one positive ionizable group, one aromatic ring as well as five excluded volumes. Fischer’s validation clearly shows that proposed Hypo 1 has highly predictive ability and can be efficiently used as a 3D query for virtual screening to retrieve potential inhibitors from ZINC databases. The hit compounds sub- sequently were docked into the DPP-Ⅳ active site and 21 compounds were obtained based on PLP2 scoring function. Therefore, this study could provide scientific basis for denovo design of DPP-Ⅳ inhibitors. Keywords: Type Ⅱ Diabetes; Dipeptidyl-Peptidase IV; Pharmacophore Model; Database Searching DPP-Ⅳ抑制剂三维药效团模型构建* 1 1# 2 1 1 2