title: Increased affinity and selectivity of enkephalin tripeptide (Tyr-D-Ala-Gly) dimers.
abstract: The binding of alkylendiamide dimers of the three N-terminal residues of [D-Ala2,D-Leu5]enkephalin (DADL) to rat brain and Ng108-15 neuroblastoma-glioma cell membranes was compared with that of DADL, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol (DAGO) and morphiceptin. Tritiated DADL and DAGO were used as labeled ligands for delta- and mu-receptors, respectively. Dimerization of the tripeptides resulted in dramatic increases in both mu and delta binding. The binding to mu-receptors showed two peaks at an alkyl chain length of n = 2 and approximately n = 16. In contrast, delta binding (NG108-15 cells) increased steadily with increasing chain length. The dimers with n less than 18 were mu-preferential, and the one with n = 2 showed the most dramatic increase in mu selectivity with a 400 fold higher affinity to mu- than to delta-receptors. For long-chain alkyl spacers the compounds became delta selective.
authors.forename: R A
authors.initials: RA
authors.lastname: Lutz
authors.forename: R A
authors.initials: RA
authors.lastname: Cruciani
authors.forename: Y
authors.initials: Y
authors.lastname: Shimohigashi
authors.forename: T
authors.initials: T
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Kassis
authors.forename: P J
authors.initials: PJ
authors.lastname: Munson
authors.forename: D
authors.initials: D
authors.lastname: Rodbard
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu
chemical_list: D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu