Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two δ‐opioid receptor active peptide families, are reported. A number of DPLPE‐deltorphin chimeric peptides have been synthesized in which the C‐terminal dipeptide δ‐address of the deltorphins (‐Val‐GlyNH2, ‐Nle‐GlyNH2) have been linked to the highly δ‐opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at §‐receptors when the C‐terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C‐terminal dipeptides retained high δ‐selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for δ‐selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine‐4 with p‐chlorophenylalanine‐4 did not increase δ‐selectivity as in DPDPE. These findings suggest that the δ‐receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.
|Original language||English (US)|
|Number of pages||5|
|Journal||International journal of peptide and protein research|
|State||Published - Jul 1994|
- opioid peptides
ASJC Scopus subject areas