[D-Met2,Pro5] enkephalin [N1.5-beta-D-glucopyranosyl] amide: a glycosylpeptide with high antinociceptive activity

Int J Pept Protein Res. 1988 May;31(5):474-80. doi: 10.1111/j.1399-3011.1988.tb00906.x.

Abstract

Different synthetic strategies have been attempted for the synthesis of a glycosylpeptide resulting from the covalent bonding of a sugar residue to the C-terminal carboxyl group of an enkephalin related pentapeptide. The final structure is: Tyr-D-Met-Gly-Phe-Pro [N1.5-beta-D-glucopyranosyl] amide. The in vitro potency on the GPI test of this analogue was IC50 = 64.0 nM. However, its antinociceptive activity by tail immersion tests, after intraperitoneal administration, was 2000 and 200 times higher than morphine in rats and mice, respectively.

MeSH terms

  • Analgesics / chemical synthesis*
  • Animals
  • Enkephalin, Methionine / analogs & derivatives*
  • Enkephalin, Methionine / chemical synthesis
  • Enkephalin, Methionine / pharmacology
  • Enkephalins*
  • Guinea Pigs
  • In Vitro Techniques
  • Indicators and Reagents
  • Male
  • Mice
  • Mice, Inbred ICR
  • Morphine / pharmacology
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Pain / physiopathology
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Enkephalins
  • Indicators and Reagents
  • enkephalin, Met(2)-ProNH2(5)(N(1.5)-glucopyranosyl)
  • Enkephalin, Methionine
  • Morphine