Ochoa De Aspuru E, Zatón A M
Departamento de Bioquímica y Biología Molecular, Universidad del País Vasco, Facultad de Farmacia, Vitoria, Spain.
J Biochem Biophys Methods. 1993 Sep;27(2):87-94. doi: 10.1016/0165-022x(93)90052-p.
Propylthiouracil is an antithyroid drug which is carried by the blood, thanks to its binding with human seroalbumin (HSA), and induces a structural alteration in HSA that changes the binding capability of other ligands. Then, with the aim of fixing the functional group in propylthiouracil involved in the interactions with HSA, the binding parameters for several uracil derivatives bound on HSA have been estimated. Interaction of propyluracil, thiouracil and propylthiouracil with HSA leads to the formation of complexes that show spectral shifts. These spectral shifts are a measure of the fraction of chromophoric groups, which is perturbed in the interaction with HSA, and thus can be used in the ligand binding estimate. The difference spectroscopy results correspond to the binding on a single centre in HSA. The difference spectra of propyluracils in seroalbumin coincide with those of propyluracils in a perturbant solvent (ethanol). On the other hand, propylthiouracil and propyluracil bind to seroalbumin on a larger scale than uracil and thiouracil. Thus, we can conclude that this binding is strengthened by hydrophobic interactions between the propyl group in propyluracils and apolar substituents on HSA.
丙硫氧嘧啶是一种抗甲状腺药物，它通过与人类血清白蛋白（HSA）结合而由血液携带，并诱导HSA发生结构改变，从而改变其他配体的结合能力。然后，为了确定丙硫氧嘧啶中参与与HSA相互作用的官能团，已估算了几种结合在HSA上的尿嘧啶衍生物的结合参数。丙基尿嘧啶、硫脲嘧啶和丙硫氧嘧啶与HSA的相互作用导致形成显示光谱位移的复合物。这些光谱位移是发色团基团分数的一种度量，其在与HSA的相互作用中受到扰动，因此可用于配体结合估算。差示光谱结果对应于在HSA中单个位点上的结合。血清白蛋白中丙基尿嘧啶的差示光谱与在扰动溶剂（乙醇）中丙基尿嘧啶的差示光谱一致。另一方面，丙硫氧嘧啶和丙基尿嘧啶比尿嘧啶和硫脲嘧啶更广泛地与血清白蛋白结合。因此，我们可以得出结论，丙基尿嘧啶中的丙基与HSA上的非极性取代基之间的疏水相互作用增强了这种结合。
