S- and C-glycopeptide derivatives of an LH-RH agonist

Int J Pept Protein Res. 1996 Jul;48(1):59-70. doi: 10.1111/j.1399-3011.1996.tb01107.x.

Abstract

The S- and C-glycosylated nonapeptides 1 and 2 were synthesized as analogs of the non-glycosylated LH-RH agonist buserelin (pGlu-His-Trp-Ser-Tyr-D-Ser(tBu)-Leu-Arg-Pro-NHEt) by segment condensation in solution. 1 and 2 differ from this peptide in the amino acid in position 6. In the first case (1), D-serine (tBu) is substituted by D-cysteine carrying a rhamnosyl residue, in the second case (2) D-alanine carrying a galactosyl moiety bound as C-glycoside is incorporated. The bioactivity of both glycopeptides as fertility drugs was determined from the dose dependent LH release in male rats. Additionally, in female rats the ovulation rate was assessed. As a result the analog 1 exhibits a similar biological activity as buserelin while analog 2 shows about 25% of this potency. Compared to buserelin the solubility of the analogs 1 and 2 in aqueous buffer is improved by more than two orders of magnitude due to the carbohydrate moieties.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / chemistry
  • Animals
  • Buserelin / analogs & derivatives*
  • Buserelin / chemistry*
  • Buserelin / pharmacology
  • Carbohydrates / chemistry
  • Cysteine / chemistry
  • Female
  • Glycopeptides / chemical synthesis*
  • Gonadotropin-Releasing Hormone / agonists*
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / drug effects
  • Luteinizing Hormone / metabolism
  • Male
  • Ovulation / drug effects
  • Protein Conformation
  • Rats
  • Structure-Activity Relationship

Substances

  • Carbohydrates
  • Glycopeptides
  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone
  • Cysteine
  • Alanine
  • Buserelin