Novel Dmt-Tic dipeptide analogues as selective delta-opioid receptor antagonists.

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.

• Authors: D Pagé, A McClory, T Mischki, R Schmidt, J Butterworth, S St-Onge, M Labarre, K Payza, W Brown
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 10 Issue 2 Pg. 167-70 (Jan 17 2000) ISSN: 0960-894X [Print] England
• PMID: 10673103 (Publication Type: Journal Article)

Chemical References

• 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

Topics

• Benzamides (metabolism)
• Binding, Competitive
• Dipeptides (chemical synthesis, pharmacology)
• Guanosine 5'-O-(3-Thiotriphosphate) (metabolism)
• Humans
• Isoquinolines (chemistry)
• Piperazines (metabolism)
• Receptors, Opioid, delta (agonists, antagonists & inhibitors)
• Tetrahydroisoquinolines
• Tyrosine (analogs & derivatives, chemistry)