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Replacement of the N-terminal Tyrosine Residue in Opioid Peptides with 3-(2,6-Dimethyl-4-carbamoylphenyl)propanoic Acid (Dcp) Results in Novel Opioid Antagonists

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journal contribution
posted on 2006-08-24, 00:00 authored by Yixin Lu, Tze Keong Lum, Yoon Wui Leow Augustine, Grazyna Weltrowska, Thi M.-D. Nguyen, Carole Lemieux, Nga N. Chung, Peter W. Schiller
3-(2,6-Dimethyl-4-carbamoylphenyl)propanoic acid (Dcp), a 2‘,6‘-dimethyltyrosine analogue containing a carbamoyl group in place of the hydroxyl function and lacking the amino group, was synthesized. The replacement of Tyr in an enkephalin analogue and in dynorphin A(1-11)-NH2 with Dcp resulted in the first opioid peptide-derived antagonists that do not contain a phenolic hydroxyl group at the 1-position residue. The cyclic peptide Dcp-c[d-Cys-Gly-Phe(pNO2)-d-Cys]NH2 represents a novel, potent μ opioid antagonist.