Delta opioid receptor-selective ligands: [D-Pen2,D-Pen5]enkephalin-dermenkephalin chimeric peptides.
A number of DPDPE-dermenkephalin chimeric peptides have been synthesized in which the putative C-terminal delta-address of dermenkephalin has been linked to the highly delta opioid selective cyclic peptide [D-Pen2,D-Pen5]enkephalin (DPDPE). Asp, Met-Asp and Leu-Met-Asp have been added to the C-terminus of DPDPE and both the carboxyl terminal and the carboxamide terminal series have been prepared. The bioassays using the mouse vas deferens and guinea pig ileum preparations have revealed a steady decrease in potency (compared to DPDPE) at delta and mu receptors as the dermenkephalin sequences were added. Some of the analogues, however, retained high delta selectivity. Similar results were obtained using radioligand binding assays. These findings suggest that the C-terminal amino acid sequence of dermenkephalin plays a role of delta-address which is specific to dermenkephalin itself, and is not additive with another delta selective ligand such as DPDPE.
Cavagnero
S
S
Department of Chemistry, University of Arizona, Tucson 85721.
Misicka
A
A
Knapp
R J
RJ
Davis
P
P
Fang
L
L
Burks
T F
TF
Yamamura
H I
HI
Hruby
V J
VJ
D000595:Amino Acid Sequence; D000818:Animals; D002678:Chimera; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000378:metabolism; D006168:Guinea Pigs; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013329:Structure-Activity Relationship
D004745:Enkephalins; D008024:Ligands; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; C059567:deltorphin; D020881:Enkephalin, D-Penicillamine (2,5)-