Abstract The main aim of this study was to characterize the molecular interaction between sulfadoxine and the major transport protein in the blood plasma, human serum albumin using fluorescence, absorption, circular dichroism, and voltammetric techniques along with computational methods. Sulfadoxine-induced changes in the fluorescence signal of human serum albumin hinted the complex formation between sulfadoxine and human serum albumin. Both values of the bimolecular quenching rate constant and UV-vis absorption spectral results characterized the quenching of human serum albumin fluorescence as static quenching. Analysis of the quenching results showed a moderate binding affinity of 3.39 × 104 M−1 at 300 K between sulfadoxine and human serum albumin. Thermodynamic data (entropy change = +104.42 J mol−1 K−1, enthalpy change = +5.25 kJ mol−1) suggested the participation of hydrophobic interactions as the main binding force in the complex formation. Secondary and tertiary structural changes along with microenvironmental perturbation around protein fluorophores were also noticed upon sulfadoxine binding. The voltammetric spectral analysis further supported the complex formation between human serum albumin and sulfadoxine. Competitive ligand displacement results, as well as computational analysis, revealed binding of sulfadoxine to Sudlow’s Site I, located in subdomain IIA of human serum albumin.

中文翻译：

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抗疟药磺胺多辛与人血清白蛋白的相互作用机制

摘要 本研究的主要目的是使用荧光、吸收、圆二色性和伏安技术以及计算方法表征磺胺多辛与血浆中主要转运蛋白、人血清白蛋白之间的分子相互作用。磺胺多辛诱导的人血清白蛋白荧光信号的变化暗示了磺胺多辛和人血清白蛋白之间的复合物形成。双分子猝灭速率常数和紫外-可见吸收光谱结果的两个值都将人血清白蛋白荧光的猝灭表征为静态猝灭。淬灭结果分析表明，磺胺多辛和人血清白蛋白在 300 K 下具有 3.39 × 104 M-1 的中等结合亲和力。热力学数据（熵变 = +104.42 J mol−1 K−1，焓变 = +5。25 kJ mol-1) 表明疏水相互作用作为复合物形成中的主要结合力。磺胺多辛结合后还注意到二级和三级结构变化以及蛋白质荧光团周围的微环境扰动。伏安光谱分析进一步支持了人血清白蛋白和磺胺多辛之间的复合物形成。竞争性配体置换结果以及计算分析揭示了磺胺多辛与位于人血清白蛋白亚域 IIA 中的 Sudlow 位点 I 的结合。伏安光谱分析进一步支持了人血清白蛋白和磺胺多辛之间的复合物形成。竞争性配体置换结果以及计算分析揭示了磺胺多辛与位于人血清白蛋白亚域 IIA 中的 Sudlow 位点 I 的结合。伏安光谱分析进一步支持了人血清白蛋白和磺胺多辛之间的复合物形成。竞争性配体置换结果以及计算分析揭示了磺胺多辛与位于人血清白蛋白亚域 IIA 中的 Sudlow 位点 I 的结合。