A. Misicka et al., DELTA-OPIOID RECEPTOR-SELECTIVE LIGANDS - DPLPE-DELTORPHIN CHIMERIC PEPTIDE ANALOGS, International journal of peptide & protein research, 44(1), 1994, pp. 80-84
Further efforts to correlate the topography of the bioactive structure
s of DPDPE and the deltorphins, two delta-opioid receptor active pepti
de families, are reported. A number of DPLPE-deltorphin chimeric pepti
des have been synthesized in which the C-terminal dipeptide delta-addr
ess of the deltorphins (-Val-GlyNH(2), -Nle-GlyNH(2)) have been linked
to the highly delta-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 re
sidue in position 5. The radioligand binding assays have revealed a de
crease in potency (compared to DPDPE) at delta-receptors when the C-te
rminal dipeptides were added to DPDPE. On the other hand, chimeric pep
tides of DPLPE with these same C-terminal dipeptides retained high del
ta-selectivity and affinity. Similar results were obtained using the m
ouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The impo
rtance of the hydrophilicity of amino acids in positions 2 and 5 for d
elta-selectivity is consistent with the previous finding for DPLPE and
DPDPE. On the other hand, the replacement of phenylalanine-4 with p-c
hlorophenylalanine-4 did not increase delta-selectivity as in DPDPE. T
hese findings suggest that the delta-receptor interacts with hybridize
d enkephalins and deltorphins somewhat differently than with DPDPE. (C
) Munksgaard 1994.