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

Cesare Giordano, Anna Sansone, Annalisa Masi, Gino Lucente, Pasqualina Punzi, Adriano Mollica, Francesco Pinnen, Federica Feliciani, Ivana Cacciatore, Peg Davis, Josephine Lai, Shou Wu Ma, Frank Porreca, Victor Hruby

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

The opioid agonists endomorphins (Tyr-Pro-Trp-Phe-NH2; EM1 and Tyr-Pro-Phe-Phe-NH2; EM2) and morphiceptin (Tyr-Pro-Phe-Pro-NH 2) exhibit an extremely high selectivity for μ-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 β-homologues of proline (HPro), of 2-pyrrolidinemethanesulphonic acid (HPrs) and of 3- pyrrolidinesulphonic acid (βPrs) have been synthesized and their binding affinity and functional activity have been investigated. The highest μ-receptor affinity is shown by [(S)βPrs2]EM2 analogue (6e) which represents the first example of a β-sulphonamido analogue in the field of opioid peptides.

Original languageEnglish (US)
Pages (from-to)4594-4600
Number of pages7
JournalEuropean journal of medicinal chemistry
Volume45
Issue number10
DOIs
StatePublished - Oct 1 2010

Keywords

  • Endomorphins
  • Opioid peptides
  • Peptide synthesis
  • Unusual amino acids
  • β-Sulphonamido peptides

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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