Enantiospecific binding of Rotigotine and its antipode to serum albumins: Investigation of binding constants and binding sites by partial-filling ACE

✍ Scribed by Bao-Lin Chu; Jin-Ming Lin; Zhihua Wang; Baoyuan Guo

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 250 KB
• Volume: 30
• Category: Article
• ISSN: 0173-0835
• DOI: 10.1002/elps.200800521

✦ Synopsis

Abstract

Enantiospecific binding of antiparkinsonian medication Rotigotine (S‐enantiomer) and its antipode to HSA or BSA was demonstrated employing partial‐filling ACE (PF‐ACE) under near‐physiological conditions (50 mM phosphate, pH 7.4, 37°C). The enantioseparation of the enantiomers was achieved by PF‐ACE. Subsequently, the binding characteristics of the enantiomers to the serum albumins were investigated. Based on the PF‐ACE data, the following binding constants were obtained: K~b,HSA,S~=8884±255 M^−1^, K~b,HSA,R~=17648±587 M^−1^, K~b,BSA,S~=7348±237 M^−1^, K~b,BSA,R~=9353±352 M^−1^. It revealed that Rotigotine had weaker affinity for the two serum albumins, and both enantiomers showed stronger affinity for HSA than BSA. The presence of either site marker (warfarin or ketoprofen) had adverse effect on the enantioseparation due to the competitive binding, or even eliminated the enantioselective binding of the enantiomers to the albumin when the molar ratio of the site marker to the albumin was at certain level. Although there might be a synergistic binding between the drug and the albumin, it was suggested that site II and I were the preferential binding site of the drug on HSA and BSA, respectively.