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.
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.
D000180:Acrylic Resins; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001681:Biological Assay; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006064:Gonadotropins, Equine / Q000494:pharmacology; D007202:Indicators and Reagents; D010060:Ovulation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D000180:Acrylic Resins; D000596:Amino Acids; D006064:Gonadotropins, Equine; D007202:Indicators and Reagents; C029456:poly-N-acrylylpyrrolidine resin; D007987:Gonadotropin-Releasing Hormone; C037440:LHRH, 1,6-cyclo(Ac-Glu(1)-Phe(2)-Trp(3)-Lys(6))-