普罗帕酮对映体与人类α1-酸性糖蛋白的相互作用。

Interaction of propafenone enantiomers with human alpha 1-acid glycoprotein.

作者信息

Oravcová J, Lindner W, Szalay P, Bohácik L, Trnovec T

机构信息

Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava, Czechoslovakia.

出版信息

Chirality. 1991;3(1):30-4. doi: 10.1002/chir.530030107.

DOI:10.1002/chir.530030107

PMID:2039682

Abstract

The interaction of propafenone enantiomers with human alpha 1-acid glycoprotein was studied using high-performance liquid chromatography. Each of the two optical antipodes interacted with one class of high-affinity binding sites characterized by Ka(R) = (6.18 +/- 0.93) x 10(5) M-1, n(R) = 1.34 +/- 0.09 for the (R)-isomer and Ka(S) = (8.93 +/- 1.82) x 10(5) M-1, n(S) = 0.99 +/- 0.08 for the (S)-isomer. Nonspecific binding to secondary low-affinity high-capacity binding site(s) was only slightly greater in the case of the (S)-enantiomer (n'k'(S) = (1.06 +/- 0.09) x 10(4) M-1) compared to the (R)-enantiomer (n'k'(R) = (6.87 +/- 0.72) x 10(3) M-1). It was concluded that both enantiomers interact with common single class of high-affinity binding sites on AAG (along with nonspecific binding) exhibiting only slight stereoselectivity for propafenone.

摘要

使用高效液相色谱法研究了普罗帕酮对映体与人类α1-酸性糖蛋白的相互作用。两种光学对映体中的每一种都与一类高亲和力结合位点相互作用，其特征在于，对于（R）-异构体，Ka（R）=（6.18±0.93）×10⁵ M⁻¹，n（R）= 1.34±0.09；对于（S）-异构体，Ka（S）=（8.93±1.82）×10⁵ M⁻¹，n（S）= 0.99±0.08。与（R）-对映体（n'k'（R）=（6.87±0.72）×10³ M⁻¹）相比，（S）-对映体与二级低亲和力高容量结合位点的非特异性结合仅略高（n'k'（S）=（1.06±0.09）×10⁴ M⁻¹）。得出的结论是，两种对映体都与AAG上常见的单一高亲和力结合位点相互作用（以及非特异性结合），对普罗帕酮仅表现出轻微的立体选择性。