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Morphological changes in human serum albumin in the presence of cationic amphiphilic drugs

机译:阳离子两亲药物存在下人血清白蛋白的形态学变化

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摘要

Human serum albumin (HSA) is one of the most important carrier proteins present in the blood and can constitute more than half of serum proteins. It transports various biomolecules including hormones, fatty acids, ions, and drugs and it functions to regulate oncotic pressure in the plasma. Cationic amphiphillic drugs like amitriptyline hydrochloride, imipramine hydrochloride and promethazine hydrochloride bind to HSA and influence its function by altering its conformation, as confirmed by Small-angle neutron scattering (SANS) data coupled with dynamic light scattering (DLS) measurements. Protein unfolding was observed by SANS results through an increase in the value of the radius of gyration Rg. At higher drug concentrations, there was no change in the dimensions of the protein. However, the drugs formed free aggregates at higher concentrations without any growth in the drug micelles, which was confirmed by the appearance of a second peak in the DLS measurements. Molecular docking revealed that the morphology of the hydrophobic moiety of the cationic amphiphilic drugs decides their binding fate with HSA, while trajectories from molecular dynamics simulations highlight structural disorder in the drug-HSA complex.
机译:人血清白蛋白(HSA)是血液中存在的最重要的载体蛋白之一,可以构成血清蛋白的一半以上。它运输各种生物分子,包括激素,脂肪酸,离子和药物,并且它起到调节血浆中的癌症压力。阳离子两亲药物,如盐酸氨米哌啶,盐酸脂蛋白氨基甲脒和盐酸丙嗪与HSA结合并通过改变其构象来影响其功能,如通过与动态光散射(DLS)测量的小角度中子散射(SAN)数据所确认的。 SAN通过增加血管半径RG的值的增加来观察蛋白质展开。在更高的药物浓度下,蛋白质的尺寸没有变化。然而,药物在较高浓度下形成自由聚集体,而没有药物胶束的任何生长,通过DLS测量中的第二峰的外观确认。分子对接表明,阳离子两亲药物的疏水部分的形态决定与HSA的结合命运,而来自分子动力学模拟的轨迹突出了药物-HSA复合物中的结构障碍。

著录项

  • 来源
    《New Journal of Chemistry》 |2018年第3期|共8页
  • 作者单位

    Islamic Univ Sci &

    Technol Dept Chem Pulwama 192122 India;

    Bhabha Atom Res Ctr Div Solid State Phys Bombay 400008 Maharashtra India;

    UCL Sch Pharm London WC1N 1AX England;

    Aligarh Muslim Univ Dept Chem Aligarh 202002 Uttar Pradesh India;

    UCL Sch Pharm London WC1N 1AX England;

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  • 正文语种 eng
  • 中图分类 化学;
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