title: Truncation of the peptide sequence in bifunctional ligands with mu and delta opioid receptor agonist and neurokinin 1 receptor antagonist activities.
abstract: The optimization and truncation of our lead peptide-derived ligand TY005 possessing eight amino-acid residues was performed. Among the synthesized derivatives, NP30 (Tyr(1)-DAla(2)-Gly(3)-Phe(4)-Gly(5)-Trp(6)-O-[3',5'-Bzl(CF3)2]) showed balanced and potent opioid agonist as well as substance P antagonist activities in isolated tissue-based assays, together with significant antinociceptive and antiallodynic activities in vivo.
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.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Tally M
authors.initials: TM
authors.lastname: Largent-Milnes
authors.forename: Scott
authors.initials: S
authors.lastname: Cowell
authors.forename: Vinod
authors.initials: V
authors.lastname: Kulkarni
authors.forename: Sharif
authors.initials: S
authors.lastname: Moye
authors.forename: Edita
authors.initials: E
authors.lastname: Navratilova
authors.forename: Peg
authors.initials: P
authors.lastname: Davis
authors.forename: Shou-Wu
authors.initials: SW
authors.lastname: Ma
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
authors.forename: Josephine
authors.initials: J
authors.lastname: Lai
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000378:metabolism
chemical_list: D000700:Analgesics; D008024:Ligands; D064729:Neurokinin-1 Receptor Antagonists; D010455:Peptides; D018040:Receptors, Neurokinin-1; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
keywords: Bifunctional compounds; NMR structure; Neutokinin-1 receptor antagonists; Opioid receptor agonists; Truncation of peptide sequence
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