Replacement of the peptide-backbone amides connecting Tyr-Gly and Gly-Gly in leucine-enkephalin with ketomethylene groups: synthesis and biological ac...
Basic Information
ID: ALA1122736
Journal: J Med Chem
Title: Replacement of the peptide-backbone amides connecting Tyr-Gly and Gly-Gly in leucine-enkephalin with ketomethylene groups: synthesis and biological activity.
Authors: Almquist RG, Olsen CM, Uyeno ET, Toll L.
Abstract: A peptide analogue of Leu-enkephalin was synthesized in which the amide linkages between Tyr-Gly and Gly-Gly were replaced by ketomethylene groups. The resulting analogue, 12, had 1/4000th and 1/2400th the opiate receptor binding activity of Leu-enkephalin when (3H) [D-Ala2,D-Leu5]enkephalin and (3H)naloxone, respectively, were used as tritiated ligands. When tested for analgesia in mice by the tail-flick assay, 12 produced analgesia in 50% of the mice tested at a dose of 24.3 micrograms/mouse (icv), while the ED50 of Leu-enkephalin is 240 micrograms/mouse (icv). At a dose of 40 micrograms/mouse (icv) or higher, 12 caused convulsions in a dose-dependent manner. No analgesia was observed after intravenous (iv) administration of 240 micrograms/mouse of 12.
CiteXplore: 6319699
DOI: 10.1021/jm00368a003
Patent ID: ┄