title: 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.
abstract: 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 Tyr1 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 mu opioid antagonist.
authors.affiliation: Department of Chemistry and Medicinal Chemistry Program, Office of Life Sciences, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore. chmlyx@nus.edu.sg
authors.forename: Yixin
authors.initials: Y
authors.lastname: Lu
authors.forename: Tze Keong
authors.initials: TK
authors.lastname: Lum
authors.forename: Yoon Wui
authors.initials: YW
authors.lastname: Leow Augustine
authors.forename: Grazyna
authors.initials: G
authors.lastname: Weltrowska
authors.forename: Thi M-D
authors.initials: TM
authors.lastname: Nguyen
authors.forename: Carole
authors.initials: C
authors.lastname: Lemieux
authors.forename: Nga N
authors.initials: NN
authors.lastname: Chung
authors.forename: Peter W
authors.initials: PW
authors.lastname: Schiller
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000737:chemistry* / Q000494:pharmacology*; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C513861:3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid; D001549:Benzamides; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010666:Phenylpropionates; C076121:2',6'-dimethyltyrosine; D014443:Tyrosine