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

A series of Dmt-Tic analogues with substitution on the Tic aromatic ring ha s been synthesized and evaluated for opioid receptor affinity and activatio n. Incorporation of large hydrophobic groups at position 7 of Tic did not g reatly 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 n M with up to 500-fold selectivity for the delta versus mu opioid receptor a nd proved to be 6 receptor antagonists. (C) 2000 Elsevier Science Ltd. All rights reserved.