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Discovery of tripeptide-derived multifunctional ligands possessing delta/mu opioid receptor agonist and neurokinin 1 receptor antagonist activities.

Authors :
Nair P
Yamamoto T
Cowell S
Kulkarni V
Moye S
Navratilova E
Davis P
Ma SW
Vanderah TW
Lai J
Porreca F
Hruby VJ
Source :
Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Sep 01; Vol. 25 (17), pp. 3716-20. Date of Electronic Publication: 2015 Jun 15.
Publication Year :
2015

Abstract

Several bifunctional peptides were synthesized and characterized based on the pentapeptide-derived ligand NP30 (1: Tyr-DAla-Gly-Phe-Gly-Trp-O-[3',5'-Bzl(CF3)2]). Modification and truncation of amino acid residues were performed, and the tripeptide-derived ligand NP66 (11: Dmt-DAla-Trp-NH-[3',5'-(CF3)2-Bzl]) was obtained based on the overlapping pharmacophore concept. The Trp(3) residue of ligand 11 works as a message residue for both opioid and NK1 activities. The significance lies in the observation that the approach of appropriate truncation of peptide sequence could lead to a tripeptide-derived chimeric ligand with effective binding and functional activities for both mu and delta opioid and NK1 receptors with agonist activities at mu and delta opioid and antagonist activity at NK1 receptors, respectively.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3405
Volume :
25
Issue :
17
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
26212775
Full Text :
https://doi.org/10.1016/j.bmcl.2015.06.030