Synthesis of tripeptides containing D-Trp substituted at the indole ring, assessment of opioid receptor binding and in vivo central antinociception

Rossella De Marco; Andrea Bedini; Santi Spampinato; Luca Gentilucci

doi:10.1021/jm5002925

Synthesis of tripeptides containing D-Trp substituted at the indole ring, assessment of opioid receptor binding and in vivo central antinociception

J Med Chem. 2014 Aug 14;57(15):6861-6. doi: 10.1021/jm5002925. Epub 2014 Jul 30.

Authors

Rossella De Marco¹, Andrea Bedini, Santi Spampinato, Luca Gentilucci

Affiliation

¹ Department of Chemistry "G. Ciamician", University of Bologna , via Selmi 2, 40126 Bologna, Italy.

PMID: 25051243
DOI: 10.1021/jm5002925

Abstract

The noncationizable tripeptide Ac-D-Trp-Phe-GlyNH2 was recently proposed as a novel minimal recognition motif for μ-opioid receptor. The introduction of different substituents (methyl, halogens, nitro, etc.) at the indole of D-Trp significantly influenced receptor affinities and resulted in serum stability and in a measurable effect on central antinociception in mice after ip administration.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Analgesics, Opioid / metabolism*
Animals
HEK293 Cells
Humans
Indoles / chemical synthesis
Indoles / chemistry*
Indoles / pharmacology
Mice
Molecular Docking Simulation
Oligopeptides / chemical synthesis
Oligopeptides / chemistry*
Oligopeptides / pharmacology
Pain Measurement
Protein Conformation
Radioligand Assay
Receptors, Opioid, delta / agonists
Receptors, Opioid, delta / metabolism
Receptors, Opioid, kappa / agonists
Receptors, Opioid, kappa / metabolism
Receptors, Opioid, mu / agonists
Receptors, Opioid, mu / metabolism
Structure-Activity Relationship
Tryptophan / analogs & derivatives*
Tryptophan / chemical synthesis
Tryptophan / chemistry*
Tryptophan / pharmacology

Substances

Analgesics, Opioid
Indoles
Oligopeptides
Receptors, Opioid, delta
Receptors, Opioid, kappa
Receptors, Opioid, mu
Tryptophan