Highly potent nociceptin analog containing the Arg-Lys triple repeat

Kazushi Okada, Tetsujo Sujaku, Yoshiro Chuman, Rie Nakashima, Takeru Nose, Tommaso Costa, Yoshinari Yamada, Masayuki Yokoyama, Atsushi Nagahisa, Yasuyuki Shimohigashi

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

One of the structural characteristics of a neuropeptide nociceptin is the existence of Arg-Lys (RK) residues at positions 8-9 and 12-13; both RKs have been suggested to bind to the acidic amino acid cluster in the second extracellular loop of the seven transmembrane domain receptor ORL1. With a design strategy of attempting to obtain an analog that binds more strongly to the receptor's acidic cluster, we synthesized a series of nociceptin analogs in which the RK dipeptide unit was placed at positions 6-7, 10-11, or 14-15 adjacent to the parent RKs. Among these nociceptin analogs containing the RK triple repeat, [ArgLys6-7]- and [Arg-Lys10-11]nociceptins exhibited weak activities (6-9 and 60-90% of nociceptin, respectively) both in the receptor binding assay and in the [35S]GTPγS binding functional assay. In contrast, [Arg-Lys14-15]nociceptin was found to be very potent in both assays (3-fold in binding and 17-fold in GTPγS functional assay). [Arg-Lys14-15]nociceptin was the first peptide analog found to be stronger than the parent nociceptin, and structure-activity studies have suggested that the incorporated Arg-Lys14-15 interacts with either the receptor acidic amino acid cluster or the receptor aromatic amino acid residues. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)493-498
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume278
Issue number2
DOIs
Publication statusPublished - Nov 19 2000

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arginyllysine
Assays
Acidic Amino Acids
Aromatic Amino Acids
nociceptin
Dipeptides
Neuropeptides

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Highly potent nociceptin analog containing the Arg-Lys triple repeat. / Okada, Kazushi; Sujaku, Tetsujo; Chuman, Yoshiro; Nakashima, Rie; Nose, Takeru; Costa, Tommaso; Yamada, Yoshinari; Yokoyama, Masayuki; Nagahisa, Atsushi; Shimohigashi, Yasuyuki.

In: Biochemical and Biophysical Research Communications, Vol. 278, No. 2, 19.11.2000, p. 493-498.

Research output: Contribution to journalArticle

Okada, K, Sujaku, T, Chuman, Y, Nakashima, R, Nose, T, Costa, T, Yamada, Y, Yokoyama, M, Nagahisa, A & Shimohigashi, Y 2000, 'Highly potent nociceptin analog containing the Arg-Lys triple repeat', Biochemical and Biophysical Research Communications, vol. 278, no. 2, pp. 493-498. https://doi.org/10.1006/bbrc.2000.3822
Okada, Kazushi ; Sujaku, Tetsujo ; Chuman, Yoshiro ; Nakashima, Rie ; Nose, Takeru ; Costa, Tommaso ; Yamada, Yoshinari ; Yokoyama, Masayuki ; Nagahisa, Atsushi ; Shimohigashi, Yasuyuki. / Highly potent nociceptin analog containing the Arg-Lys triple repeat. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 278, No. 2. pp. 493-498.
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