title: Discovery of tripeptide-derived multifunctional ligands possessing delta/mu opioid receptor agonist and neurokinin 1 receptor antagonist activities.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA.
authors.forename: Padma
authors.initials: P
authors.lastname: Nair
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Cowell
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kulkarni
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Sharif
authors.initials: S
authors.lastname: Moye
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Edita
authors.initials: E
authors.lastname: Navratilova
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Shou-Wu
authors.initials: SW
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.affiliation: Department of Pharmacology, University of Arizona, 1501 North Campbell Avenue, Tucson, AZ 85724, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Boulevard, Tucson, AZ 85721, USA. Electronic address: hruby@email.arizona.edu.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism
chemical_list: D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014364:Tryptophan
keywords: Multifunctional ligands; Neutokinin-1 receptor antagonists; Opioid receptor agonists; Truncation of peptide sequence