Binding Study of Semotiadil and Levosemotiadil with α1-Acid Glycoprotein Using High-Performance Frontal Analysis

✍ Scribed by Maria Esther Rodriguez Rosas; Akimasa Shibukawa; Yuki Yoshikawa; Yukihiro Kuroda; Terumichi Nakagawa

• Publisher: Elsevier Science
• Year: 1999
• Tongue: English
• Weight: 87 KB
• Volume: 274
• Category: Article
• ISSN: 0003-2697
• DOI: 10.1006/abio.1999.4266

✦ Synopsis

High-performance frontal analysis (HPFA) was used to investigate the binding properties of human ␣ 1 -acid glycoprotein (AGP) with semotiadil ((R)-isomer, Cachannel blocker) and its antipode levosemotiadil ((S)isomer, Ca-and Na-channel blockers). An on-line HPLC system consisting of a HPFA column, an extraction column, and an analytical HPLC column was used to determine the unbound concentrations of these enantiomers, and the experimental data were subsequently subjected to the Scatchard analyses to estimate their binding parameters. The binding affinity of the (R)-isomer (K ‫؍‬ 3.17 ؋ 10 7 M, n ‫؍‬ 0.74) is approximately 1.2 times stronger than that of (S)-isomer (K ‫؍‬ 2.59 ؋ 10 7 M, n ‫؍‬ 0.74). An enantioselective competitive binding study indicated that both enantiomers are bound at the same site on AGP molecules.