Zia H, Price J C
J Pharm Sci. 1976 Feb;65(2):226-30. doi: 10.1002/jps.2600650213.
The binding of several tetracyclines to human serum albumin was studied using difference spectrophotometry and a spectrophotometric probe, 2-(4'-hydroxybenzeneazo)benzoic acid. Difference spectra observed for the interaction between the probe and human serum albumin were similar to probe-bovine serum albumin spectra but were less intense for a given concentration of probe and did not reach saturation as quickly. Difference spectra for the tetracyclines were dependent on the characteristics of the ring substituents. More hydrophobic substituents on the D and C rings tended to give more intense difference spectra, but charge-transfer complexing may also have been involved since methacycline with a methylene group in the 6-position showed the most intense spectra of the compounds studied. Solvent perturbation, pH, and urea studies tended to confirm that something other than hydrophobic binding of the tetracyclines was involved. Drug-probe displacement studies showed that methacycline gave the greatest probe displacement followed by doxycycline, chlortetracycline, oxytetracycline, and tetracycline. This order of displacement of the anionic probe indicates that both hydrophobic and charge-transfer binding are involved. Experiments with calcium ion and ethylenediaminetetraacetic acid showed that the difference spectra obtained with the tetracyclines and human serum albumin were not the result of metallic bridge-chelate formation.
使用差示分光光度法和分光光度探针2-(4'-羟基苯偶氮)苯甲酸研究了几种四环素与人血清白蛋白的结合情况。观察到的探针与人血清白蛋白相互作用的差示光谱与探针 - 牛血清白蛋白光谱相似，但对于给定浓度的探针，其强度较低，且未像牛血清白蛋白那样快速达到饱和。四环素的差示光谱取决于环取代基的特性。D环和C环上更多的疏水取代基往往会产生更强的差示光谱，但由于在研究的化合物中，6位带有亚甲基的甲烯土霉素显示出最强的光谱，所以电荷转移络合作用可能也参与其中。溶剂扰动、pH值和尿素研究倾向于证实，四环素的结合除了疏水作用外还涉及其他因素。药物 - 探针置换研究表明，甲烯土霉素导致的探针置换最大，其次是多西环素、金霉素、土霉素和四环素。阴离子探针的这种置换顺序表明疏水结合和电荷转移结合都参与其中。钙离子和乙二胺四乙酸的实验表明，四环素与人血清白蛋白获得的差示光谱不是金属桥 - 螯合物形成的结果。
