Zatón A, Martinez A, Manuel de Gandarias J
Departamento de Bioquimica, Colegio Universitario de Alava-Universidad del Pais Vasco, Vitoria, Spain.
Biochem Pharmacol. 1988 Aug 15;37(16):3127-31. doi: 10.1016/0006-2952(88)90310-3.
The binding interactions of some thioureylene compounds to human serum albumin were studied in vitro by ultraviolet spectroscopy and equilibrium dialysis. Binding of 6-n-propyl-2-thiouracil, 6-n-benzyl-2-thiouracil and 2-thiouracil to human serum albumin results in a red shift of the ultraviolet absorption maximum, suggesting that the binding site is a hydrophobic area of the protein. Bindings of 6-n-propyl-2-thiouracil and 6-n-benzyl-2-thiouracil to human serum albumin are characterized by two classes of sites while 6-n-propyl-uracil and 2-thiouracil bind to one low-affinity binding site. In addition, an identification of those sites was performed by measuring the displacement of these drugs. The data show that the moderate-affinity site is common with the warfarin site while the low-affinity site is likely to be shared by benzodiazepines. It is concluded that the binding is enhanced by the hydrophobicity of the substituent in the thioureylene compounds, and it is further shown that thiol-group substitutions in the thioureylene ring will weaken the binding.
通过紫外光谱法和平衡透析法在体外研究了一些硫脲类化合物与人血清白蛋白的结合相互作用。6-正丙基-2-硫尿嘧啶、6-正苄基-2-硫尿嘧啶和2-硫尿嘧啶与人血清白蛋白的结合导致紫外吸收最大值发生红移，这表明结合位点是蛋白质的疏水区域。6-正丙基-2-硫尿嘧啶和6-正苄基-2-硫尿嘧啶与人血清白蛋白的结合具有两类结合位点的特征，而6-正丙基尿嘧啶和2-硫尿嘧啶则结合到一个低亲和力结合位点。此外，通过测量这些药物的置换来鉴定这些位点。数据表明，中等亲和力位点与华法林位点相同，而低亲和力位点可能为苯二氮䓬类药物所共有。得出的结论是，硫脲类化合物中取代基的疏水性增强了结合作用，并且进一步表明硫脲环中的巯基取代会削弱结合作用。
