Cyclic enkephalin analogs that are hybrids of DPDPE-related peptides and metenkephalin-Arg-Gly-Leu: prohormone analogs that retain good potency and selectivity for delta opioid receptors.
We report here on the binding affinity and bioassay results of cyclic enkephalin analogs comprising a cyclic moiety and C-terminal fragment of MERGL, where ME denotes methionine enkephalin. MERGL (YGGFMRGL) has been suggested to be cleaved enzymatically by membrane-bound enkephalinase 24.11 to leave ME and the tripeptide RGL. In our study we have synthesized hybrids of DPDPE or DPLCE and the C-terminal tripeptide RGL in order to mimic a prohormone able to cross the blood-brain barrier. The study has shown that of the homologs presented here, analogs of DPLCE often are more potent at delta opioid receptors both in binding affinity and in bioactivity at the MVD, than DPDPE. Our hypothesis that hybrids (consisting of the drug and the spacer for the carrier) could be designed which would either have no opioid activity or, alternatively, be by themselves very active, has been verified.
Bartosz-Bechowski
H
H
Department of Chemistry, University of Arizona, Tucson 85721, USA.
Davis
P
P
Slaninova
J
J
Malatynska
E
E
Stropova
D
D
Porreca
F
F
Yamamura
H I
HI
Hruby
V J
VJ
D000818:Animals; D001681:Biological Assay; D002626:Chemistry, Pharmaceutical; D004594:Electrophysiology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004744:Enkephalin, Methionine / Q000138:chemical synthesis*; D004745:Enkephalins / Q000138:chemical synthesis*; D006168:Guinea Pigs; D007082:Ileum / Q000737:chemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010452:Peptide Biosynthesis; D011485:Protein Binding; D011498:Protein Precursors / Q000138:chemical synthesis*; D017465:Receptors, Opioid, delta / Q000737:chemistry*; D014649:Vas Deferens / Q000737:chemistry
D004745:Enkephalins; D011498:Protein Precursors; D017465:Receptors, Opioid, delta; D004744:Enkephalin, Methionine; D020881:Enkephalin, D-Penicillamine (2,5)-