Truncation of the peptide sequence in bifunctional ligands with mu and delta opioid receptor agonist and neurokinin 1 receptor antagonist activities.

TitleTruncation of the peptide sequence in bifunctional ligands with mu and delta opioid receptor agonist and neurokinin 1 receptor antagonist activities.
Publication TypeJournal Article
Year of Publication2013
AuthorsNair P, Yamamoto T, Largent-Milnes TM, Cowell S, Kulkarni V, Moye S, Navratilova E, Davis P, Ma S-W, Vanderah TW, Lai J, Porreca F, Hruby VJ
JournalBioorg Med Chem Lett
Volume23
Issue17
Pagination4975-8
Date Published2013 Sep 1
ISSN1464-3405
KeywordsAmino Acid Sequence, Analgesics, Animals, Humans, Ligands, Neurokinin-1 Receptor Antagonists, Peptides, Rats, Receptors, Neurokinin-1, Receptors, Opioid, delta, Receptors, Opioid, mu
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.
DOI10.1016/j.bmcl.2013.06.065
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID23899615
PubMed Central IDPMC3810412
Grant ListDA-06284 / DA / NIDA NIH HHS / United States
DA-13449 / DA / NIDA NIH HHS / United States
P01 DA006284 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
Faculty Member Reference: 
Victor Hruby, Ph.D.
Josephine Lai , Ph.D.
Tally Largent-Milnes, PhD
Edita Navratilova
Frank Porreca, PhD
Todd Vanderah, PhD