Abstract
A series of Dmt-Tic analogues with substitution on the Tic aromatic ring has been synthesized and evaluated for opioid receptor affinity and activation. Incorporation of large hydrophobic groups at position 7 of Tic did not greatly alter the delta opioid receptor binding affinities of the dipeptides whereas substitution at position 6 substantially diminished their affinity. These modified Dmt-Tic peptides showed binding affinities as low as 2.5 nM with up to 500-fold selectivity for the delta versus mu opioid receptor and proved to be delta receptor antagonists.
MeSH terms
-
Benzamides / metabolism
-
Binding, Competitive
-
Dipeptides / chemical synthesis*
-
Dipeptides / pharmacology
-
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
-
Humans
-
Isoquinolines / chemistry*
-
Piperazines / metabolism
-
Receptors, Opioid, delta / agonists
-
Receptors, Opioid, delta / antagonists & inhibitors*
-
Tetrahydroisoquinolines*
-
Tyrosine / analogs & derivatives*
-
Tyrosine / chemistry
Substances
-
Benzamides
-
Dipeptides
-
Isoquinolines
-
Piperazines
-
Receptors, Opioid, delta
-
Tetrahydroisoquinolines
-
2',6'-dimethyltyrosine
-
4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide
-
1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
-
Guanosine 5'-O-(3-Thiotriphosphate)
-
Tyrosine