Tyrosine411 and Arginine410 of Human Serum Albumin Play an Important Role in the Binding of Sodium 4-Phenylbutyrate to Site II

Taisuke Enokida, Keishi Yamasaki, Yuko Okamoto, Kazuaki Taguchi, Takako Ishiguro, Toru Maruyama, Hakaru Seo, Masaki Otagiri

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Sodium 4-phenylbutyrate (PB) has many pharmacological activities; therefore extending its clinical use to the treatment of a wider variety of diseases would be desirable. However, our knowledge of the binding of PB to plasma proteins is not extensive. To address this issue in more detail, we characterized the protein binding of PB. Binding experiments showed that PB mainly binds to human serum albumin (HSA) in plasma. PB was also found to bind to a single site on HSA, which was identified as site II by fluorescent probe displacement experiment. Furthermore, an appropriate alkyl chain length and a carboxylic group in the PB structure were required for PB binding to HSA, suggesting that hydrophobic (and van der Waals) and electrostatic interactions are involved as binding modes. The contributions of hydrogen bonding and/or van der Waals interactions were also indicated by thermodynamic analyses. Tyrosine411 and arginine410 were identified as being involved in the binding of PB to site II, based on binding experiments using chemically modified- and mutant-HSA preparations. In conclusion, the available evidence indicates that PB binds to site II of HSA with assistance by multiple forces and that tyrosine411 and arginine410 both play important roles in this phenomenon.

本文言語English
ページ(範囲)1987-1994
ページ数8
ジャーナルJournal of Pharmaceutical Sciences
105
6
DOI
出版ステータスPublished - 2016 6月 1
外部発表はい

ASJC Scopus subject areas

  • 薬科学

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