Institute of Chemistry, Technology, and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, Njegoševa 12, 11000 Belgrade, Serbia.
Faculty of Chemistry, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia.
Molecules. 2024 Sep 20;29(18):4474. doi: 10.3390/molecules29184474.
Secondary polyphenol metabolites, urolithins (UROs), have anti-oxidative, anti-inflammatory, and antidiabetic properties. Therefore, their biological activity relies on blood transport via human serum albumin (HSA) and tissue distribution. The main goal we set was to investigate the interaction between HSA and different URO (URO A, URO B, URO C, URO D, and glucuronidated URO A and B) using a combination of multi-spectroscopic instrumental and in silico approaches. The fluorescence spectroscopy revealed that URO can quench the naturally occurring fluorescence of HSA in a concentration-dependent manner. The HSA fluorescence was quenched by both a static and dynamic mechanism. The results showed that free UROs bind to HSA with higher affinity than their conjugated forms. CD spectroscopy and FTIR revealed that the alpha-helical structure of HSA is preserved. The calculated Gibbs free energy change indicates that the URO-HSA complex forms spontaneously. There is a single binding site on the HSA surface. The molecular docking results indicated that unconjugated Uro binds to Sudlow I, while their conjugation affects this binding site, so in the conjugated form, they bind to the cleft. Docking experiments indicate that all UROs are capable of binding to both thyroxine recognition sites of ligand-bound HSA proteins. Examining interactions under the following conditions (298 K, 303 K, and 310 K, pH 7.4) is of great importance for determining the pharmacokinetics of these bioactive compounds, as the obtained results can be used as a basis for modulating the potential dosing regimen.
次级多酚代谢物，尿石素（UROs）具有抗氧化、抗炎和抗糖尿病的特性。因此，它们的生物活性依赖于通过人血清白蛋白（HSA）的血液转运和组织分布。我们的主要目标是使用多种光谱仪器和计算方法相结合来研究 HSA 与不同 URO（URO A、URO B、URO C、URO D 和葡萄糖醛酸化的 URO A 和 B）之间的相互作用。荧光光谱表明，URO 可以以浓度依赖的方式猝灭 HSA 中天然存在的荧光。HSA 的荧光被静态和动态机制猝灭。结果表明，游离 URO 与 HSA 的结合亲和力高于其共轭形式。CD 光谱和 FTIR 表明 HSA 的α-螺旋结构得以保留。计算得到的吉布斯自由能变化表明 URO-HSA 复合物自发形成。HSA 表面有一个单一的结合位点。分子对接结果表明，未共轭的 Uro 结合到 Sudlow I 上，而它们的共轭会影响这个结合位点，因此在共轭形式下，它们结合到裂隙中。对接实验表明，所有 URO 都能够结合到配体结合的 HSA 蛋白的两个甲状腺素识别位点上。在以下条件（298 K、303 K 和 310 K，pH 7.4）下研究相互作用对于确定这些生物活性化合物的药代动力学非常重要，因为获得的结果可以作为调节潜在给药方案的基础。
