Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin.
Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin.
复制标题
4-苯基丁酸钠与血清白蛋白结合的物种差异。
DOI：
10.1016/j.xphs.2017.04.025
复制
发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Otagiri M.
中科院分区：
文献类型：
--
作者：
Yamasaki K;Enokida T;Taguchi K;Miyamura S;Kawai A;Miyamoto S;Maruyama T;Seo H;Otagiri M.
4-苯基丁酸钠（PB）是临床上用于治疗尿素循环障碍的药物。最近的研究表明，PB还具有其他药理活性，这表明它有可能用作治疗其他疾病的药物。在药物开发过程中，需要使用实验动物进行临床前试验，以验证PB的有效性和安全性。虽然PB与人白蛋白的结合已经研究，但我们对其与其他动物种属白蛋白结合的了解非常有限。为了解决这一问题，我们的特点是结合PB白蛋白从几个物种（人，牛，兔，大鼠）。结果表明，PB与来自这些物种的白蛋白的1个高亲和力位点相互作用，该位点对应于人白蛋白的位点II。PB对人白蛋白和牛白蛋白的亲和力高于对兔白蛋白和大鼠白蛋白的亲和力，对兔白蛋白的亲和力最低。使用PB的结构相关化合物的结合和分子对接研究表明，亲和力的物种差异归因于白蛋白上PB结合位点的结构特征的差异（例如，电荷分布、疏水性、形状或尺寸）。
Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle disorders. Recent research has shown that PB also has other pharmacologic activities, suggesting that it has the potential for use as a drug for treating other disorders. In the process of drug development, preclinical testing using experimental animals is necessary to verify the efficacy and safety of PB. Although the binding of PB to human albumin has been studied, our knowledge of its binding to albumin from the other animal species is extremely limited. To address this issue, we characterized the binding of PB to albumin from several species (human, bovine, rabbit, and rat). The results indicated that PB interacts with 1 high-affinity site of albumin from these species, which corresponds to site II of human albumin. The affinities of PB to human and bovine albumins were higher than those to rabbit and rat albumin, and that to rabbit albumin was the lowest. Binding and molecular docking studies using structurally related compounds of PB suggested that species differences in the affinity are attributed to differences in the structural feature of the PB-binding sites on albumins (e.g., charge distribution, hydrophobicity, shape, or size).