title: Topographical requirements for delta opioid ligands: presence of a carboxyl group in position 4 is not critical for deltorphin high delta receptor affinity and analgesic activity.
abstract: To investigate the role of the carboxyl group in deltorphin molecules, we have synthesized three new analogues in which the acidic amino acid residues in position 4 of the deltorphins were replaced by non-acidic but hydrophilic amino acids residues. The three analogues, [Ser4]-, [Gln4]-, and [Cys4]-deltorphin, all are as potent or more potent than either deltorphin I or II at delta opioid receptors and possess good delta selectivities. The excellent correlation between their in vitro delta receptor potencies and their intrathecal antinociception activity forms a strong argument for involvement of those receptors in spinal nociceptive modulation in the rats.
authors.affiliation: Department of Chemistry, University of Arizona, Tucson 85721.
authors.forename: A
authors.initials: A
authors.lastname: Misicka
authors.forename: A W
authors.initials: AW
authors.lastname: Lipkowski
authors.forename: L
authors.initials: L
authors.lastname: Fang
authors.forename: R J
authors.initials: RJ
authors.lastname: Knapp
authors.forename: P
authors.initials: P
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Kramer
authors.forename: T F
authors.initials: TF
authors.lastname: Burks
authors.forename: H I
authors.initials: HI
authors.lastname: Yamamura
authors.forename: D B
authors.initials: DB
authors.lastname: Carr
authors.forename: V J
authors.initials: VJ
authors.lastname: Hruby
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000737:chemistry*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010146:Pain; D011487:Protein Conformation; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta
chemical_list: D000700:Analgesics; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-