Itoh T, Nakashima K, Tsuda Y, Yamada H
Department of Pharmacokinetics and Biopharmaceutics, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Chirality. 1996;8(2):201-6. doi: 10.1002/(SICI)1520-636X(1996)8:2<201::AID-CHIR5>3.0.CO;2-L.
Binding of carbenicillin (CBPC) epimers to human serum albumin (HSA) was found to be stereoselective. Epimer-epimer interaction was also observed in the binding to HSA. There were at least three binding sites on HSA for CBPC epimers, one of which (stereoselective site) was more in favor of S-CBPC than R-CBPC. At the stereoselective site, the binding constant of S-CBPC was approximately 4-fold greater than that of R-CBPC. The affinities to other binding sites (non-stereoselective sites) were similar between the epimers, and the affinity of S-CBPC of the non-stereoselective sites was much smaller than that for the stereoselective site. R-CBPC and S-CBPC appeared to displace each other at all the binding sites, i.e., the binding of the epimers was competitive at the non-stereoselective sites as well as at the stereoselective site. By using site marker ligands, it was revealed that CBPC epimers may bind to Site I (warfarin binding site), but not to Site II (diazepam binding site). A binding model with an assumption of competitive interactions at all the binding sites simulated the binding characteristics of CBPC epimers fairly well.
发现羧苄青霉素（CBPC）差向异构体与人血清白蛋白（HSA）的结合具有立体选择性。在与HSA的结合中还观察到差向异构体-差向异构体相互作用。HSA上至少有三个CBPC差向异构体的结合位点，其中一个（立体选择性位点）对S-CBPC的偏好高于R-CBPC。在立体选择性位点，S-CBPC的结合常数约为R-CBPC的4倍。差向异构体对其他结合位点（非立体选择性位点）的亲和力相似，且非立体选择性位点的S-CBPC亲和力远小于立体选择性位点。R-CBPC和S-CBPC似乎在所有结合位点相互取代，即差向异构体在非立体选择性位点以及立体选择性位点的结合都是竞争性的。通过使用位点标记配体，发现CBPC差向异构体可能与位点I（华法林结合位点）结合，但不与位点II（地西泮结合位点）结合。一个假设所有结合位点都存在竞争性相互作用的结合模型很好地模拟了CBPC差向异构体的结合特性。
