摘要
成纤维细胞激活蛋白(FAP)与肿瘤微血管的形成和肿瘤的生长密切相关,是药物设计的理想靶点。本文运用分子对接分析51个(4-喹啉)-甘氨酰-氰基吡咯烷衍生物与FAP受体的相互作用,研究结果表明吡咯烷衍生物与FAP受体ASP46、THR51、GLN721等氨基酸残基形成氢键和立体作用。采用比较分子力场分析(Co MFA)和比较分子相似性指数分析(Co MSIA)组合场进行3D-QSAR研究。Co MFA和Co MSIA模型的q2及r2分别为0.821,0.967和0.710,0.951,3D-QSAR结果表明模型具有较强的预测能力。3D-QSAR等势图显示小分子的立体、静电、疏水、氢键等性质影响生物活性,与分子对接结果一致,为设计出更高活性吡咯烷类抑制剂提供借鉴。
FAP involved in the formation of tumor microvascular and tumor growth was an ideal target for drug design. In this paper,the interaction of 51(4-Quinolinoyl)glycyl-2-cyanopyrrolidine scaffold derivatives and the FAP receptor based on the Surflex-dockwas studied. The result showed that pyrrolidine derivatives combine with FAP receptor amino acid residues ASP46,THR51,GLN721with hydrrgen bond and steric interactien. Then the combined field of CoMFA and CoMSIA was used to analyze 3D-QSAR models.The model(CoMFA with q2 = 0. 821,r2 = 0. 967,n = 5;CoMSIA with q2 = 0. 710,r2 = 0. 951,n = 4)had a good predictability. 3DQSARcontour maps indicated the steric,electrostatic,hydrophobic and hydrogen bond fields had a crucial effects to derivatives biologicalactivity,which in common with Surflex-Dock result. These datum provided significant theoretical foundation for designingpyrrolidine scaffold derivatives inhibitors.
作者
汪斌
常自超
舒茂
王远强
林勇
林治华
WANG Bin;CHANG Zi-chao;SHU Mao;WANG Yuan-qiang;LIN Yong;LIN Zhi-hua(School of Pharmacy and Bioengineering,Chongqing University of Technology,Chongqing 400054,China;School of Chemistry and Chemical Engineering,Chongqing University,Chongqing 400044,China)
出处
《化学研究与应用》
CAS
CSCD
北大核心
2016年第7期947-953,共7页
Chemical Research and Application
基金
国家自然科学基金项目(81171508)资助
重庆市自然科学基金重点项目(CSTC 2013 JJB10004)资助
重庆市教委科技项目(KJ1500943
KJ1400946)资助
