Differential receptor binding characteristics of consecutive phenylalanines in μ-opioid specific peptide ligand endomorphin-2

Takeshi Honda, Naoto Shirasu, Kaname Isozaki, Michiaki Kawano, Daiki Shigehiro, Yoshiro Chuman, Tsugumi Fujita, Takeru Nose, Yasuyuki Shimohigashi

研究成果: Contribution to journalArticle査読

15 被引用数 (Scopus)

抄録

Endogenous opioid peptides consist of a conserved amino acid residue of Phe3 and Phe4, although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the μ opioid receptor, possesses two Phe residues at the consecutive positions 3 and 4. In order to clarify the role of Phe3 and Phe4 in binding to the μ receptor, we synthesized a series of analogs in which Phe3 and Phe4 were replaced by various amino acids. It was found that the aromaticity of the Phe-β-phenyl groups of Phe3 and Phe4 is a principal determinant of how strongly it binds to the receptor, although better molecular hydrophobicity reinforces the activity. The receptor binding subsites of Phe3 and Phe4 of endomorphin-2 were found to exhibit different structural requirements. The results suggest that [Trp3]endomorphin-2 (native endomorphin-1) and endomorphin-2 bind to different receptor subclasses.

本文言語英語
ページ(範囲)3883-3888
ページ数6
ジャーナルBioorganic and Medicinal Chemistry
15
11
DOI
出版ステータス出版済み - 6 1 2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子医療
  • 分子生物学
  • 薬科学
  • 創薬
  • 臨床生化学
  • 有機化学

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