title: Novel C-terminus modifications of the Dmt-Tic motif: a new class of dipeptide analogues showing altered pharmacological profiles toward the opioid receptors.
abstract: The design, synthesis and pharmacological evaluation of a novel class of Dmt-Tic dipeptide analogues are described. These resulting analogues bearing different C-terminal functionalities were found to bind to the human delta receptor with high affinity. One specific class of dipeptides bearing urea/thiourea functionalities showed partial to full activation of the delta receptor. Several dipeptides also showed good binding affinities with full activation of the human kappa receptor, a novel property for those ligands.
authors.affiliation: Departments of Chemistry and Pharmacology, AstraZeneca R&D Montreal, 7171 Frederick-Banting, Saint-Laurent, Quebec, Canada H4S 1Z9. daniel.page@astrazeneca.com
authors.forename: D
authors.initials: D
authors.lastname: Pagé
authors.forename: A
authors.initials: A
authors.lastname: Naismith
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
authors.forename: M
authors.initials: M
authors.lastname: Coupal
authors.forename: M
authors.initials: M
authors.lastname: Labarre
authors.forename: M
authors.initials: M
authors.lastname: Gosselin
authors.forename: D
authors.initials: D
authors.lastname: Bellemare
authors.forename: K
authors.initials: K
authors.lastname: Payza
authors.forename: W
authors.initials: W
authors.lastname: Brown
mesh_terms: D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism*; D044005:Tetrahydroisoquinolines; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry*
chemical_list: D004151:Dipeptides; D007546:Isoquinolines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D044005:Tetrahydroisoquinolines; C076121:2',6'-dimethyltyrosine; C078986:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D014443:Tyrosine