Synthesis and changes in affinity for NOP and opioid receptors of novel hexapeptides containing β(2)-tryptophan analogues

Bioorg Med Chem Lett. 2013 Jul 15;23(14):4052-5. doi: 10.1016/j.bmcl.2013.05.064. Epub 2013 May 28.

Abstract

We report the synthesis and the biological activity of new analogues of Ac-RFMWMK-NH2 and Ac-RYYRWK-NH2, modified in position 4 and 5, respectively, with incorporation of newly synthesized β(2)-tryptophan analogues. Trp was substituted by the (S)-2-(1-methyl-1H-indol-3-yl)propionic residue or by (S)-2-(5-methoxy-1H-indol-3-yl)propionic residue. The biological activity (pEC50 and Emax) of these compounds was tested on electrically stimulated preparations of rat vas deferens. The 5-methoxy β-tryptophan group reverses the affinity of the compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Male
  • Nociceptin Receptor
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Oligopeptides / pharmacology
  • Protein Binding
  • Rats
  • Receptors, Opioid / chemistry*
  • Receptors, Opioid / metabolism
  • Tryptophan / chemistry*
  • Vas Deferens / drug effects

Substances

  • Oligopeptides
  • Receptors, Opioid
  • Tryptophan
  • Nociceptin Receptor
  • Oprl protein, rat