Synthesis and activity of endomorphin-2 and morphiceptin analogues with proline surrogates in position 2

Eur J Med Chem. 2010 Oct;45(10):4594-600. doi: 10.1016/j.ejmech.2010.07.022. Epub 2010 Jul 21.

Abstract

The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH(2); EM1 and Tyr-Pro-Phe-Phe-NH(2); EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH(2)) exhibit an extremely high selectivity for mu-opioid receptor. Here a series of novel EM2 and morphiceptin analogues containing in place of the proline at position 2 the S and R residues of beta-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3-pyrrolidinesulphonic acid (betaPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest micro-receptor affinity is shown by [(S)betaPrs(2)]EM2 analogue (6e) which represents the first example of a beta-sulphonamido analogue in the field of opioid peptides.

Publication types

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

MeSH terms

  • Analgesics, Opioid / chemical synthesis
  • Analgesics, Opioid / chemistry*
  • Analgesics, Opioid / pharmacology*
  • Cell Line
  • Endorphins / chemical synthesis
  • Endorphins / chemistry*
  • Endorphins / pharmacology*
  • Humans
  • Oligopeptides / chemical synthesis
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Proline / analogs & derivatives
  • Proline / chemical synthesis
  • Proline / pharmacology
  • Protein Binding
  • Receptors, Opioid / agonists
  • Receptors, Opioid / metabolism*
  • Receptors, Opioid, mu / agonists
  • Receptors, Opioid, mu / metabolism

Substances

  • Analgesics, Opioid
  • Endorphins
  • Oligopeptides
  • Receptors, Opioid
  • Receptors, Opioid, mu
  • endomorphin 2
  • morphiceptin
  • Proline