[Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3629-31. doi: 10.1016/j.bmcl.2016.06.003. Epub 2016 Jun 3.

Abstract

Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment.

Keywords: Bifunctional opioid/antioxidant peptides; Neuropathic pain; Opioid activity profiles; Tyrosine analogues; [Dmt(1)]DALDA.

Publication types

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

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology*
  • Receptors, Opioid, mu / agonists*
  • Structure-Activity Relationship

Substances

  • 2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide
  • Oligopeptides
  • Receptors, Opioid, mu