Effects of substitution of hydrophobic amino acids by tryptophan on receptor binding and biological activity of neuropeptide nociceptin

Kazushi Okada, Tetsujo Sujaku, Rie Nakashima, Takeru Nose, Yoshinari Yamada, Masayuki Yokoyama, Atushi Nagahisa, Yasuyuki Shimohigashi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nociceptin is a neuropeptide that binds to and activates the opioid receptor-like ORL1 receptor. In order to explore the structural elements necessary for receptor recognition and activation, we designed and synthesized a series of nociceptin analogues, in which nonpolar amino acid residues such as Gly6, Ala7, Ala11, Leu14, and Ala15 were substituted respectively by Trp. [Trp6]- and [Trp7]-nociceptins exhibited rather weak activities (5-15% of nociceptin), and [Trp11]- and [Trp15]-nociceptins also showed reduced activities (40-50%). These results suggested that the space available for these particular residues are relatively restricted. By contrast, the Trp/Leu-substitution at position 14 retained full receptor binding activity, and the resulting [Trp14]nociceptin exhibited an increased biological activity in the functional assay using [35S]GTPγS. This suggested that the receptor residue interacting with nociceptin-Leu14 is the aromatic amino acid.

Original languageEnglish
Pages (from-to)1899-1904
Number of pages6
JournalBulletin of the Chemical Society of Japan
Volume72
Issue number8
DOIs
Publication statusPublished - Aug 1 1999

All Science Journal Classification (ASJC) codes

  • Chemistry(all)

Fingerprint Dive into the research topics of 'Effects of substitution of hydrophobic amino acids by tryptophan on receptor binding and biological activity of neuropeptide nociceptin'. Together they form a unique fingerprint.

  • Cite this