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

J Med Chem. 2006 Aug 24;49(17):5382-5. doi: 10.1021/jm060369k.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis
  • Benzamides / chemistry*
  • Benzamides / pharmacology*
  • Molecular Structure
  • Narcotic Antagonists*
  • Opioid Peptides / chemistry*
  • Opioid Peptides / pharmacology*
  • Phenylpropionates / chemical synthesis
  • Phenylpropionates / chemistry*
  • Phenylpropionates / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tyrosine / analogs & derivatives*
  • Tyrosine / chemistry

Substances

  • 3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid
  • Benzamides
  • Narcotic Antagonists
  • Opioid Peptides
  • Phenylpropionates
  • 2',6'-dimethyltyrosine
  • Tyrosine