title: New 2',6'-dimethyl-L-tyrosine (Dmt) opioid peptidomimetics based on the Aba-Gly scaffold. Development of unique mu-opioid receptor ligands.
abstract: The Aba-Gly scaffold, incorporated into Dmt-Tic ligands (H-Dmt-Tic-Gly-NH-CH2-Ph, H-Dmt-Tic-Gly-NH-Ph, H-Dmt-Tic-NH-CH2-Bid), exhibited mixed micro/delta or delta opioid receptor activities with micro agonism. Substitution of Tic by Aba-Gly coupled to -NH-CH2-Ph (1), -NH-Ph (2), or -Bid (Bid=1H-benzimidazole-2-yl) (3) shifted affinity (Ki(micro)=0.46, 1.48, and 19.9 nM, respectively), selectivity, and bioactivity to micro-opioid receptors. These compounds represent templates for a new class of lead opioid agonists that are easily synthesized and suitable for therapeutic pain relief.
authors.affiliation: Department of Organic Chemistry, Vrije Universiteit Brussels, Pleinlaan 2, B-1050 Brussels, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Ballet
authors.forename: Severo
authors.initials: S
authors.lastname: Salvadori
authors.forename: Claudio
authors.initials: C
authors.lastname: Trapella
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Bryant
authors.forename: Yunden
authors.initials: Y
authors.lastname: Jinsmaa
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Lazarus
authors.forename: Lucia
authors.initials: L
authors.lastname: Negri
authors.forename: Elisa
authors.initials: E
authors.lastname: Giannini
authors.forename: Roberta
authors.initials: R
authors.lastname: Lattanzi
authors.forename: Dirk
authors.initials: D
authors.lastname: Tourwé
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Balboni
mesh_terms: D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D018716:Molecular Mimicry; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009197:Myenteric Plexus / Q000502:physiology; D010455:Peptides / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D001552:Benzazepines; D008024:Ligands; D010455:Peptides; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D005998:Glycine