Tsuda Y, Tsunoi T, Watanabe N, Ishida M, Yamada H, Itoh T
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Chirality. 2001 May 15;13(5):236-43. doi: 10.1002/chir.1025.
Binding of sulbenicillin (SBPC) isomers to human serum albumin (HSA) was stereoselective. There were at least two classes of binding sites on HSA for SBPC isomers. At the stereoselective high affinity site, binding was in favor of R-SBPC, the binding constant of R-SBPC being approximately 2.3-fold greater than that of S-SBPC. By using site marker ligands, it was revealed that the stereoselective site was Site I (warfarin binding site). Affinity for the low affinity (nonstereoselective) site was similar for the diastereomers, approximately 7--30-fold lower than for the stereoselective site. R-SBPC and S-SBPC appeared to displace each other competitively at both binding sites. On the other hand, R-SBPC was degraded much faster than S-SBPC in the presence of HSA, with a degradation rate constant approximately 7-fold greater for R-SBPC than for S-SBPC. The degradation of R-SBPC was inhibited in the presence of warfarin and dependent on the concentration of R-SBPC bound to Site I. The results demonstrate that Site I is responsible for the stereoselective degradation.
磺苄西林（SBPC）异构体与人血清白蛋白（HSA）的结合具有立体选择性。HSA上存在至少两类用于SBPC异构体的结合位点。在立体选择性高亲和力位点，R-SBPC更易结合，其结合常数约为S-SBPC的2.3倍。通过使用位点标记配体，发现立体选择性位点为位点I（华法林结合位点）。两种非对映体对低亲和力（非立体选择性）位点的亲和力相似，比对立体选择性位点的亲和力低约7至30倍。R-SBPC和S-SBPC在两个结合位点上似乎相互竞争取代。另一方面，在有HSA存在的情况下，R-SBPC的降解速度比S-SBPC快得多，R-SBPC的降解速率常数约为S-SBPC的7倍。在有华法林存在的情况下，R-SBPC的降解受到抑制，且依赖于与位点I结合的R-SBPC的浓度。结果表明位点I是立体选择性降解的原因。
