The biological activity and metabolic stability of peptidic bifunctional compounds that are opioid receptor agonists and neurokinin-1 receptor antagonists with a cystine moiety

Bioorg Med Chem. 2009 Oct 15;17(20):7337-43. doi: 10.1016/j.bmc.2009.08.035. Epub 2009 Aug 21.

Abstract

In order to improve metabolic stability, a ring structure with a cystine moiety was introduced into TY027 (Tyr-D-Ala-Gly-Phe-Met-Pro-Leu-Trp-NH-[3',5'-(CF(3))(2)Bzl]), which is a lead compound of our developing bifunctional peptide possessing opioid agonist and NK1 antagonist activities. TY038 (Tyr-cyclo[D-Cys-Gly-Phe-Met-Pro-D-Cys]-Trp-NH-[3',5'-(CF(3))(2)Bzl]) was found as a highly selective delta opioid agonist over mu receptor in conventional tissue-based assays, together with an effective NK1 antagonist activity and good metabolic stability with more than 24h half life in rat plasma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cystine / chemistry*
  • Half-Life
  • In Vitro Techniques
  • Neurokinin-1 Receptor Antagonists*
  • Peptides / chemistry
  • Peptides / pharmacokinetics
  • Peptides / pharmacology*
  • Rats
  • Receptors, Opioid / agonists*

Substances

  • Neurokinin-1 Receptor Antagonists
  • Peptides
  • Receptors, Opioid
  • Cystine