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: R A Lutz, R A Cruciani, Y Shimohigashi, T Costa, S Kassis, P J Munson, D Rodbard
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 111 Issue 2 Pg. 257-61 (May 08 1985) ISSN: 0014-2999 [Print] Netherlands
• PMID: 2990953 (Publication Type: Journal Article)

Chemical References

• Enkephalins
• Oligopeptides
• Receptors, Opioid
• Receptors, Opioid, delta
• Receptors, Opioid, mu

Topics

• Animals
• Brain (metabolism)
• Enkephalins (metabolism)
• In Vitro Techniques
• Male
• Oligopeptides (metabolism)
• Rats
• Rats, Inbred Strains
• Receptors, Opioid (metabolism)
• Receptors, Opioid, delta
• Receptors, Opioid, mu