Synthesis, characterization and nociceptive screening of new VV-hemorphin-5 analogues

Bioorg Med Chem Lett. 2018 Oct 1;28(18):3073-3079. doi: 10.1016/j.bmcl.2018.07.040. Epub 2018 Jul 30.

Abstract

In the present study, some new analogues of VV-hemorphin-5, modified at position 1 and 7 by the non-proteinogenic and/or natural amino acids followed the structures Xxx-Val-Val-Tyr-Pro-Trp-Thr-Gln-NH2 and Val-Val-Tyr-Pro-Trp-Thr-Yyy-NH2, where Xxx is Ile or Aib and Yyy is Lys/Orn/Dap/Dab were synthesized to investigate their potential antinociceptive activities. We report also the redox potentials and the acid/base properties as pKa values of these peptide analogues which were compared toward electrochemical behaviour of tryptophan containing peptides. All analogues showed a short lasting initial antinociceptive effect, however H2 hemorphin analogue is characterized with prolong and strong antinociceptive effect, while the other peptide analogues exerted more variable effects on the visceral nociception depending on the dose or time after the intracerebral injection.

Keywords: Antinociceptive activity; Hemorphin analogues; Opioid peptides; Unnatural amino acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / administration & dosage
  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Analgesics / chemical synthesis
  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Animals
  • Behavior, Animal / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Hemoglobins / chemical synthesis
  • Hemoglobins / chemistry
  • Hemoglobins / pharmacology*
  • Infusions, Intraventricular
  • Mice
  • Molecular Structure
  • Pain / drug therapy*
  • Pain Measurement
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Analgesics
  • Hemoglobins
  • Peptide Fragments
  • VV-hemorphin-5