Stereoselective binding and degradation of sulbenicillin in the presence of human serum albumin
Article first published online: 12 APR 2001
Copyright © 2001 Wiley-Liss, Inc.
Volume 13, Issue 5, pages 236–243, 2001
How to Cite
Tsuda, Y., Tsunoi, T., Watanabe, N., Ishida, M., Yamada, H. and Itoh, T. (2001), Stereoselective binding and degradation of sulbenicillin in the presence of human serum albumin. Chirality, 13: 236–243. doi: 10.1002/chir.1025
- Issue published online: 12 APR 2001
- Article first published online: 12 APR 2001
- Manuscript Accepted: 18 JAN 2001
- Manuscript Received: 5 OCT 2000
- β-lactam antibiotic;
- protein binding;
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. Chirality 13:236–243, 2001. © 2001 Wiley-Liss, Inc.