Format

Send to

Choose Destination
J Med Chem. 2008 Sep 25;51(18):5866-70. doi: 10.1021/jm8004702.

Novel opioid peptide derived antagonists containing (2S)-2-methyl-3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid [(2S)-Mdcp].

Author information

1
Department of Chemistry and Medicinal Chemistry Program, Office of Life Sciences, National University of Singapore, 3 Science Drive 3, Singapore.

Abstract

A synthesis of the novel tyrosine analogue (2 S)-2-methyl-3-(2,6-dimethyl-4-carbamoylphenyl)propanoic acid [(2 S)-Mdcp] (15) was developed. In (2 S)-Mdcp, the amino and hydroxyl groups of 2',6'-dimethyltyrosine are replaced by a methyl and a carbamoyl group, respectively, and its substitution for Tyr (1) in opioid agonist peptides resulted in compounds showing antagonism at all three opioid receptors. The cyclic peptide (2 S)-Mdcp-c[D-Cys-Gly-Phe(pNO 2)-D-Cys]NH 2 (1) was a potent and selective mu antagonist, whereas (2 S)-Mdcp-c[D-Pen-Gly-Phe(pF)-Pen]-Phe-OH (3) showed subnanomolar delta antagonist activity and extraordinary delta selectivity.

PMID:
18800771
PMCID:
PMC2630426
DOI:
10.1021/jm8004702
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center