戊乙奎醚光学异构体与毒蕈碱型受体亚型的分子对接研究

发布时间：2018-05-30 09:48

本文选题：戊乙奎醚 + 光学异构体　；参考：《中国药房》2017年25期

【摘要】：目的:研究戊乙奎醚光学异构体对毒蕈碱型(M)受体亚型的亲和性,为揭示戊乙奎醚的作用靶点及药效选择性提供参考。方法:利用同源建模和分子对接等分子模拟技术,通过比较戊乙奎醚不同光学异构体R1(3R,2′R)、R2(3R,2′S)、S1(3S,2′R)和S2(3S,2′S)与M受体亚型M_1~M_5的结合能,判断其与M受体亚型的亲和性。结果:戊乙奎醚4个光学异构体均能够对接到M受体各亚型的活性位点,不同异构体与不同M受体亚型的分子对接显示出较大差异。4个光学异构体与M_3受体具有较大的结合能,在5 736.519~5 907.143 kcal/mol之间;R1与M_1的结合能为1 190.04 kcal/mol;而其他光学异构体与各受体亚型的结合能较低或为负数。结论:戊乙奎醚的异构体R1对M_1受体具有亲和性,4个光学异构体均对M_3受体具有亲和性。
[Abstract]:Aim: to study the affinity of the optical isomers of pentehyclidine to muscarinic M) receptor subtypes, and to provide a reference for revealing the target and pharmacodynamic selectivity of pentehyclidine. Methods: by means of homology modeling and molecular docking techniques, the binding energies of different optical isomers R1, R1, R3, R2, R2, R2, R2, S1, S1, S1, S1, S1, S1, S1, S1, S1, S2, S2, S2, S2, S2, S2S-, and S2S-, and S2S- (2), were compared, and their affinity to M-receptor subtype M_1~M_5 was determined by comparing their binding energies with M-receptor subtype. Results: all of the four optical isomers of pentanethionine could connect to the active sites of each subtype of M receptor, the molecular docking of different isomers with different subtypes of M receptor showed great differences, and the four optical isomers had great binding energy with M3 receptor. At 5736.519 ~ 5 907.143 kcal/mol, the binding energy of R1 to MK-1 was 1 190.04 kcal / mol, while the binding energy of other optical isomers to each receptor subtype was lower or negative. Conclusion: the isomer R1 of penehyclidine has affinity to M _ 1 receptor, and all four optical isomers have affinity to M _ S _ 3 receptor.
【作者单位】：四川省医学科学院/四川省人民医院药学部;四川大学华西医院肿瘤中心生物治疗实验室;
【基金】：四川省医学科学院/四川省人民医院青年科研基金(No.30305030606) 四川大学-泸州市人民政府战略合作资金项目(No.2015CDLZ-S10) 电子科技大学中央高校基本科研业务(No.ZYGX2015J14)
【分类号】：R914

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