Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin

Keishi Yamasaki, Taisuke Enokida, Kazuaki Taguchi, Shigeyuki Miyamura, Akito Kawai, Shuichi Miyamoto, Toru Maruyama, Hakaru Seo, Masaki Otagiri

研究成果: Article

3 引用 (Scopus)

抜粋

Sodium 4-phenylbutyrate (PB) is clinically used as a drug for treating urea cycle disorders. Recent research has shown that PB also has other pharmacologic activities, suggesting that it has the potential for use as a drug for treating other disorders. In the process of drug development, preclinical testing using experimental animals is necessary to verify the efficacy and safety of PB. Although the binding of PB to human albumin has been studied, our knowledge of its binding to albumin from the other animal species is extremely limited. To address this issue, we characterized the binding of PB to albumin from several species (human, bovine, rabbit, and rat). The results indicated that PB interacts with 1 high-affinity site of albumin from these species, which corresponds to site II of human albumin. The affinities of PB to human and bovine albumins were higher than those to rabbit and rat albumin, and that to rabbit albumin was the lowest. Binding and molecular docking studies using structurally related compounds of PB suggested that species differences in the affinity are attributed to differences in the structural feature of the PB-binding sites on albumins (e.g., charge distribution, hydrophobicity, shape, or size).

元の言語English
ページ(範囲)2860-2867
ページ数8
ジャーナルJournal of Pharmaceutical Sciences
106
発行部数9
DOI
出版物ステータスPublished - 2017 9 1
外部発表Yes

    フィンガープリント

ASJC Scopus subject areas

  • Pharmaceutical Science

これを引用

Yamasaki, K., Enokida, T., Taguchi, K., Miyamura, S., Kawai, A., Miyamoto, S., Maruyama, T., Seo, H., & Otagiri, M. (2017). Species Differences in the Binding of Sodium 4-Phenylbutyrate to Serum Albumin. Journal of Pharmaceutical Sciences, 106(9), 2860-2867. https://doi.org/10.1016/j.xphs.2017.04.025