Zeder-Lutz G, Van Regenmortel M H, Wenger R, Altschuh D
Institut de Biologie Moléculaire et Cellulaire du CNRS, Laboratoire d'Immunochimie, Strasbourg, France.
J Chromatogr B Biomed Appl. 1994 Dec 9;662(2):301-6. doi: 10.1016/0378-4347(94)00211-8.
The immunosuppressant drug cyclosporin A exists as various conformers in water. Up to 1 h is needed to reach maximum complex formation after mixing the drug with its receptor, cyclophilin, or an antibody, indicating that only a fraction of the conformers in aqueous solution adopts a conformation suitable for binding. In the present study we compare the binding behavior of cyclosporin to that of two analogs, using a biosensor instrument (BIAcore, Pharmacia). The amount of complex formation was measured as a function of time after adding the peptides to cyclophilin. The equilibrium affinity constants of cyclophilin for these analogs have been measured. The slow binding of cyclosporin to cyclophilin compared to the instant binding of the cyclosporin analogs supports the hypothesis that cyclophilin recognizes a well defined conformation of cyclosporin that exists in water prior to binding.
免疫抑制剂环孢菌素A在水中以多种构象形式存在。将该药物与其受体亲环蛋白或抗体混合后，需要长达1小时才能达到最大复合物形成，这表明水溶液中只有一部分构象适合结合。在本研究中，我们使用生物传感器仪器（BIAcore，Pharmacia）比较了环孢菌素与其两种类似物的结合行为。将肽添加至亲环蛋白后，测量复合物形成量随时间的变化。已测量了亲环蛋白对这些类似物的平衡亲和常数。与环孢菌素类似物的即时结合相比，环孢菌素与亲环蛋白的缓慢结合支持了这样一种假设，即亲环蛋白识别环孢菌素在结合前在水中存在的一种明确构象。
