Synthesis of [1, 6-cyclo (acetyl-1-L-glutamic acid, 2-D-phenylalanine, 3-D-tryptophan, 6-D-lysine)] luteinizing hormone-releasing hormone on poly-N-acrylylpyrrolidine resin

Int J Pept Protein Res. 1983 Feb;21(2):127-34. doi: 10.1111/j.1399-3011.1983.tb03086.x.

Abstract

The protected peptide, Ac-Glu(OBut)-D-Phe-D-Trp-Ser(But)-Tyr(But)-D-Lys (Z)-Leu-Arg(Tos)-Pro-Gly-NH2 was synthesized in a stepwise manner on a resin of poly-N-acrylylpyrrolidine using both acid cleavable N alpha-tert.-butyloxycarbonyl and base cleavable N alpha-fluorenylmethyloxycarbonyl protecting groups. After cleavage by ammonolysis in methanol, the tert.-butyl and benzyloxy-carbonyl side-chain protecting groups were cleaved with CF3-CO2H-thioanisole and the 1-6 amide ring formed by cyclization with diphenylphosphorylazide, after which the remaining tosyl protecting group was cleaved in HF-anisole. [1,6-Cyclo(Ac-Glu1, D-Phe2, D-Trp3, D-Lys6]LH-RH exhibited less than 10% of the antiovulatory potency of [D less than Glu1, D-Phe2, D-Trp3,6] LH-RH, a potent linear antagonist.

MeSH terms

  • Acrylic Resins*
  • Amino Acids / analysis
  • Animals
  • Biological Assay
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / chemical synthesis
  • Gonadotropin-Releasing Hormone / pharmacology
  • Gonadotropins, Equine / pharmacology
  • Indicators and Reagents
  • Ovulation / drug effects
  • Rats
  • Rats, Inbred Strains

Substances

  • Acrylic Resins
  • Amino Acids
  • Gonadotropins, Equine
  • Indicators and Reagents
  • poly-N-acrylylpyrrolidine resin
  • Gonadotropin-Releasing Hormone
  • LHRH, 1,6-cyclo(Ac-Glu(1)-Phe(2)-Trp(3)-Lys(6))-