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烯唑醇与血清蛋白的立体选择性作用机制

陈冉 郭栋 何汝坚 殷霞 范军 章伟光

陈冉, 郭栋, 何汝坚, 殷霞, 范军, 章伟光. 烯唑醇与血清蛋白的立体选择性作用机制[J]. 华南师范大学学报(自然科学版), 2022, 54(2): 30-36. doi: 10.6054/j.jscnun.2022023
引用本文: 陈冉, 郭栋, 何汝坚, 殷霞, 范军, 章伟光. 烯唑醇与血清蛋白的立体选择性作用机制[J]. 华南师范大学学报(自然科学版), 2022, 54(2): 30-36. doi: 10.6054/j.jscnun.2022023
CHEN Ran, GUO Dong, HE Rujian, YIN Xia, FAN Jun, ZHANG Weiguang. Understanding the Stereoselective Mechanism of Diniconazole Enantiomers Interacting with Serum Albumins[J]. Journal of South China normal University (Natural Science Edition), 2022, 54(2): 30-36. doi: 10.6054/j.jscnun.2022023
Citation: CHEN Ran, GUO Dong, HE Rujian, YIN Xia, FAN Jun, ZHANG Weiguang. Understanding the Stereoselective Mechanism of Diniconazole Enantiomers Interacting with Serum Albumins[J]. Journal of South China normal University (Natural Science Edition), 2022, 54(2): 30-36. doi: 10.6054/j.jscnun.2022023

烯唑醇与血清蛋白的立体选择性作用机制

doi: 10.6054/j.jscnun.2022023
基金项目: 

广东省自然科学基金项目 2018A030313193

详细信息
    通讯作者:

    范军,Email: fanj@scnu.edu.cn

    章伟光,Email: wgzhang@scnu.edu.cn

  • 中图分类号: O657.3

Understanding the Stereoselective Mechanism of Diniconazole Enantiomers Interacting with Serum Albumins

  • 摘要: 手性药物与血清蛋白的结合通常表现出立体选择性。采用UV-Vis吸收光谱、荧光光谱和分子对接技术研究了R-烯唑醇和S-烯唑醇与人血清蛋白(HSA)/牛血清蛋白(BSA)的结合差异。结果表明:血清蛋白与R-烯唑醇的结合能力强于S-烯唑醇;烯唑醇对血清蛋白的荧光猝灭机制为静态猝灭;R-烯唑醇和S-烯唑醇与HSA相互作用的总能量分别为-26.4 kJ/mol和-23.6 kJ/mol,与BSA的对接能量分别为-27.6 kJ/mol和-23.3 kJ/mol,说明R-烯唑醇与血清蛋白形成的复合物更稳定。研究结果可为后续开展烯唑醇的立体选择性作用机制研究提供依据。
  • 图  1  烯唑醇对映异构体的分子结构

    Figure  1.  The molecular structures of diniconazole enantiomers

    图  2  不同烯唑醇对映体的浓度对HSA和BSA紫外吸收光谱的影响

    注:曲线编号0→8代表血清蛋白溶液中烯唑醇的浓度从0逐步增加为1.0、2.0、3.0、4.0、5.0、6.0、7.0、8.0 μmol/L。

    Figure  2.  The effect of different concentrations of diniconazole enantiomers on the UV-Vis spectra of HSA and BSA

    图  3  HSA和BSA在加入烯唑醇对映体前后的荧光光谱

    注:曲线编号0→5代表血清蛋白溶液中烯唑醇的浓度从0逐步增加为6.1、15.3、30.7、46.0和61.3 μmol/L。

    Figure  3.  The fluorescent spectra of HSA and BSA without/with diniconazole enantiomers

    图  4  不同温度下烯唑醇与HSA、BSA的Stern-Volmer图

    Figure  4.  The Stern-Volmer plots of diniconazole with HSA and BSA at different temperatures

    图  5  HSA-烯唑醇和BSA-烯唑醇复合物的分子对接结果

    注:图A~D分别显示烯唑醇在HSA或BSA中的结合位点,放大图给出了烯唑醇与相邻氨基酸残基结合力的详细说明。

    Figure  5.  The molecular docking results of the HSA- and BSA-diniconazole complexes

    表  1  不同温度下HSA和BSA与烯唑醇对映体的结合常数(Ka)、结合位点数(n)和热力学参数

    Table  1.   The binding constant (Ka), number of binding sites (n) and relative thermodynamic parameters of HSA and BSA with diniconazole enantiomers at different temperatures

    作用体系 T/K Stern-Volmer方程 双对数方程 范特霍夫方程
    KSV/
    (L·mol-1)
    kq/
    (L·mol-1·s-1)
    R2 Ka/
    (L·mol-1)
    n R2 ΔH/
    (kJ·mol-1)
    ΔG/
    (kJ·mol-1)
    ΔS/
    (J·mol-1·K-1)
    R2
    HSA与R-烯唑醇 293 0.95×105 0.95×1013 0.945 7 74.31×105 1.60 0.994 8 -91.4 -13.5 -265.90 0.996 4
    303 1.31×105 1.31×1013 0.993 2 3.51×105 1.21 0.997 5 -9.8 -269.44
    313 1.62×105 1.62×1013 0.988 9 0.30×105 1.07 0.965 5 -1.2 -254.86
    HSA与S-烯唑醇 293 0.93×105 0.93×1013 0.952 3 22.08×105 1.56 0.991 2 -94.0 -15.5 -268.23 0.987 7
    303 1.16×105 1.16×1013 0.991 1 0.81×105 1.21 0.998 1 -17.3 -253.25
    313 1.29×105 1.29×1013 0.989 6 0.08×105 0.95 0.979 5 -12.8 -259.69
    BSA与R-烯唑醇 293 0.97×105 0.97×1013 0.946 8 79.78×105 1.66 0.994 9 -74.9 -13.6 -209.03 0.982 9
    303 1.32×105 1.32×1013 0.993 6 4.01×105 1.26 0.999 2 -11.1 -210.60
    313 1.64×105 1.64×1013 0.991 1 0.53×105 1.12 0.983 4 -12.3 -199.98
    BSA与S-烯唑醇 293 0.93×105 0.93×1013 0.950 9 22.96×105 1.56 0.993 3 -74.9 -15.5 -202.72 0.989 6
    303 1.17×105 1.17×1013 0.989 7 1.68×105 1.21 0.998 1 -17.4 -189.79
    313 1.33×105 1.33×1013 0.988 3 0.25×105 1.07 0.993 6 -13.6 -195.84
    下载: 导出CSV

    表  2  HSA-烯唑醇和BSA-烯唑醇复合物的分子对接参数

    Table  2.   The molecular docking parameters for binding between HSA- and BSA-diniconazole complexes

    作用体系 疏水相互作用 氢键 π-阳离子相互作用 对接能量/
    (kJ·mol-1)
    残基 距离/nm 残基 距离/nm 残基 距离/nm
    HSA与R-烯唑醇 ARG117 0.342 ARG117 0.252 ARG117 0.441 -26.4
    ILE142 0.365 ARG117 0.232
    TYR161 0.349 LEU182 0.201
    ARG186 0.322
    HSA与S-烯唑醇 ILE142 0.334 TYR161 0.219 -23.6
    PHE157 0.381 LEU185 0.195
    ARG186 0.384 GLY189 0.337
    ARG186 0.397
    BSA与R-烯唑醇 LEU454 0.324 THR190 0.194 ARG458 0.454 -27.6
    TYR451 0.326 SER428 0.217
    ILE455 0.336 TYR451 0.303
    TYR451 0.338
    GLU186 0.344
    BSA与S-烯唑醇 LYS431 0.344 GLU186 0.198 -23.3
    TYR451 0.309 LEU189 0.202
    ILE455 0.349 THR190 0.295
    ILE455 0.378
    下载: 导出CSV
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出版历程
  • 收稿日期:  2021-04-26
  • 网络出版日期:  2022-05-12
  • 刊出日期:  2022-04-25

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