A Tetrameric Enkephalin Analog for the Putative Multivalent Interaction with Opioid Receptors

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Author(s)

    • KONDO Michio
    • Department of Chemistry, Faculty of Science and Engineering, Saga University
    • KITAJIMA Hiroshi
    • Department of Chemistry, Faculty of Science and Engineering, Saga University
    • YASUNAGA Teruo
    • Department of Chemistry, Faculty of Science and Engineering, Saga University
    • KODAMA Hiroaki
    • Department of Chemistry, Faculty of Science and Engineering, Saga University

Abstract

Based on increased affinity and selectivity of dimeric enkephalin analogs for opioid receptors, divalent interactions have been demonstrated between opioid peptides and receptors. To explore the receptor multivalency suggested by fluorescent microscopic studies, a novel type of tetrameric enkephalin analog was designed and synthesized. The tetrameric enkephalin comprises four [<FONT SIZE="-2">D</FONT>-Ala<sup>2</sup>, Leu<sup>5</sup>]enkephalin molecules coupled with the amino groups of the <i>gem</i>-diamino derivative of cystine, which was derived from cysteinamide by a Hofmann-type rearrangement, causing an amide-to-amine conversion. By the reduction of the <i>gem</i>-cystine disulfide bond in the tetramer, two dimeric analogs with a free or <i>p</i>-methoxybenzyl-protected mercapto group were also prepared. The receptor binding characteristics of these tetramer and dimers for the <i>δ</i> and <i>μ</i> receptors were analyzed in an NG108-15 cell and rat-brain membranes. The affinity of the tetrameric analog for the <i>δ</i> receptors was about equal to that of the dimers, but 2—4-fold lower for the <i>μ</i> receptors. The dimers were 5—8-fold <i>δ</i>-selective, and, thus, the tetramer exhibited a high selectivity for the <i>δ</i> receptors. A divalent interaction mechanism was considered between the tetrameric ligand and the <i>δ</i> opioid receptors.

Journal

  • Bulletin of the Chemical Society of Japan

    Bulletin of the Chemical Society of Japan 68(11), 3161-3167, 1995-11-15

    The Chemical Society of Japan

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Codes

  • NII Article ID (NAID)
    10008895141
  • NII NACSIS-CAT ID (NCID)
    AA00580132
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00092673
  • Data Source
    CJP  J-STAGE 
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