[Cyclic] [D-Pen2,D-Pen5]enkephalin analogs with increased affinity and selectivity for .delta.-opioid receptors

The conformationally restricted, cyclic disulfide-containing enkephalin analogue [D-Pen2,D-Pen5]enkephalin (DPDPE) was modified by halogenation (F, Cl, Br, I) of the phenylalanine-4 residue in the para position. The potency and selectivity of these analogues for the delta opioid receptor was greater...

Full description

Saved in:
Bibliographic Details
Published in:Journal of medicinal chemistry 1990-01, Vol.33 (1), p.249-253
Main Authors: Toth, Geza, Kramer, Thomas H, Knapp, Richard, Lui, George, Davis, Peg, Burks, Thomas F, Yamamura, Henry I, Hruby, Victor J
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Aminoacids, peptides. Hormones. Neuropeptides
Analytical, structural and metabolic biochemistry
Animals
Biological and medical sciences
Brain - metabolism
Chemical Phenomena
Chemistry
Enkephalin, D-Penicillamine (2,5)
Enkephalins - chemical synthesis
Enkephalins - metabolism
Enkephalins - pharmacology
Fundamental and applied biological sciences. Psychology
Guinea Pigs
Ileum - physiology
Male
Mice
Molecular Sequence Data
Muscle Contraction - drug effects
Proteins
Radioligand Assay
Rats
Receptors, Opioid - drug effects
Receptors, Opioid - physiology
Receptors, Opioid, delta
Structure-Activity Relationship
Vas Deferens - physiology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The conformationally restricted, cyclic disulfide-containing enkephalin analogue [D-Pen2,D-Pen5]enkephalin (DPDPE) was modified by halogenation (F, Cl, Br, I) of the phenylalanine-4 residue in the para position. The potency and selectivity of these analogues for the delta opioid receptor was greater than that of the parent peptide. The analogues possessed greater potency and affinity for the delta receptors than DPDPE in the mouse vas deferens assay and in radioreceptor assays (against [3H]DPDPE), respectively. [p-ClPhe4]DPDPE was the most selective in the radioligand binding assays (IC50(mu)/IC50(delta) = 574), being about 5-fold more delta opioid receptor selective than DPDPE in this assay, whereas [p-IPhe4]DPDPE was the most selective in the classical bioassay systems using the mouse vas deferens and guinea pig ileum assays (IC50(GPI)/IC50(MVD) = 17,374), making it nearly 9-fold more selective than DPDPE in direct comparisons using the same assay conditions.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00163a041