Šunderić Miloš, Šukalović Vladimir, Penezić Ana, Nikolić Milan R, Nedić Olgica, Minić Simeon, Četić Danilo, Gligorijević Nikola
Department of Biochemistry, Institute for the Application of Nuclear Energy, University of Belgrade, Belgrade, Serbia.
Department of Chemistry, University of Belgrade - Institute of Chemistry, Technology, and Metallurgy, National Institute of the Republic of Serbia, Belgrade, Serbia.
J Biomol Struct Dyn. 2025 Feb 3:1-13. doi: 10.1080/07391102.2025.2460087.
Poor bioavailability and reduced stability are the main drawbacks to efficiently utilizing many naturally occurring antioxidants, so their binding to circulatory proteins is essential. This work investigated whether major human circulatory proteins, besides albumin, including transferrin, alpha-2-macroglobulin, and fibrinogen, bind widely consumed antioxidants and food supplements, including quercetin, resveratrol, and dihydrolipoic acid, thus filling the gap of detailed pharmacokinetic properties of these food supplements. Detailed examination of the protein structural and functional changes that occur upon ligand binding was analyzed by spectroscopic methods and docking and molecular dynamic simulation studies on the model that consists of the protein/antioxidant pair with the highest affinity constant. It was found that alpha-2-macroglobulin binds resveratrol with the highest affinity ( of 4.5 x 10 M). results revealed four potential binding sites between -resveratrol and alpha-2-macroglobulin, with hydrogen bonds being crucial for binding, while other observed interactions (primarily aromatic interactions) are of secondary importance. The binding of resveratrol to alpha-2-macroglobulin leads to mutual protection of both molecules from oxidative stress and significantly increased hidrosolubility of resveratrol, both of which could serve to increase the bioavailability and bioactivity of resveratrol in circulation.
生物利用度低和稳定性降低是有效利用许多天然抗氧化剂的主要缺点，因此它们与循环蛋白的结合至关重要。这项研究调查了除白蛋白外的主要人类循环蛋白，包括转铁蛋白、α-2-巨球蛋白和纤维蛋白原，是否会结合广泛食用的抗氧化剂和食品补充剂，包括槲皮素、白藜芦醇和二氢硫辛酸，从而填补这些食品补充剂详细药代动力学特性的空白。通过光谱方法以及对具有最高亲和常数的蛋白质/抗氧化剂对模型进行对接和分子动力学模拟研究，分析了配体结合后发生的蛋白质结构和功能变化的详细情况。研究发现，α-2-巨球蛋白与白藜芦醇的结合亲和力最高（为4.5×10 M）。结果揭示了反式白藜芦醇与α-2-巨球蛋白之间的四个潜在结合位点，氢键对结合至关重要，而其他观察到的相互作用（主要是芳香族相互作用）则次要。白藜芦醇与α-2-巨球蛋白的结合导致两个分子相互免受氧化应激的影响，并显著提高了白藜芦醇的水溶性，这两者都有助于提高白藜芦醇在循环中的生物利用度和生物活性。
