STAT3与环烷烃并噻吩类衍生物抑制剂的分子对接  

Molecular docking of STAT3 and cycloalkanethiophene derivatives inhibitors

作　　者：高鸿雁 史丽颖[1] 宋昱 曹洪玉[1] 于大永[1] GAO Hongyan;SHI Liying;SONG Yu;CAO Hongyu;YU Dayong(School of Life Science and Technology,Dalian University,Dalian 116622,Liaoning Province,China)

机构地区：[1]大连大学生命科学与技术学院,辽宁大连116622

出　　处：《天津师范大学学报（自然科学版）》2022年第5期32-37,共6页Journal of Tianjin Normal University：Natural Science Edition

基　　金：辽宁省科学技术计划资助项目(2019-ZD-0564).

摘　　要：为了探究2-氨基-3-氰基噻吩衍生物类小分子对信号传导和转录激活因子3(STAT3)的抑制作用机理,选取52个新型的2-氨基-3-氰基噻吩衍生物类小分子为靶向抑制剂,基于分子对接技术,分析STAT3靶向抑制剂与STAT3的SH2结构域的相互作用模式.结果表明:2-氨基-3-氰基噻吩衍生物类抑制剂与STAT3有良好的亲和力,主要作用方式为氢键、疏水、π-cation、静电以及极性作用.对配体-受体相互作用氨基酸残基进行分析,发现了8个关键氨基酸:Lys591、Arg609、Ser611、Glu612、Ser613、Val637、Glu638、Pro639.与STAT3晶体结构中的原配体相比,小分子52#虽然能较好地进入蛋白表面的活性空腔,但受分子大小与形状的影响,未能深入活性口袋中的侧面空腔.因此在未来设计STAT3相关药物时,增加分子大小使小分子形成“桥梁”状结构可能会提升STAT3抑制剂的活性.In order to explore the inhibition mechanism of 2-amino-3-cyanothiophene derivatives on signal transducer and activator of transcription 3(STAT3),52 new 2-amino-3-cyanothiophene derivatives were adopted as targeting inhibitors.Based on molecular docking technology,the domain binding mode of STAT3 targeting inhibitors and SH2 in STAT3 was analyzed.The results show that 2-amino-3-cyanothiophene derivatives have good affinity with STAT3,and the main interaction modes include hydrogen bonding,hydrophobicity,π-cation,static electricity and polar effects.Analysis of the amino acid residues involved in the interaction of the small molecule-receptor binding region revealed eight important amino acids:Lys591,Arg609,Ser611,Glu612,Ser613,Val637,Glu638,Pro639.In addition,compared with the original ligand in the crystal structure of STAT3,though the small molecule 52#can enter the active cavity of protein surface,but failed to enter the lateral cavity due to the size and shape of the molecule.Therefore,in the design of related drugs in the future,increasing the size of molecules to make small molecules form a"bridge"-like structure may be beneficial to the improvement of the activity of STAT3 inhibitors.

关 键 词：信号传导和转录激活因子3(STAT3) 2-氨基-3-氰基噻吩衍生物 抑制剂 分子对接 作用方式 

分 类 号：R914[医药卫生—药物化学]