Analogues of luteinizing hormone releasing factor modified at positions 2, 6, and 10

J Med Chem. 1976 Jul;19(7):937-41. doi: 10.1021/jm00229a016.

Abstract

Eighteen analogues of luteinizing hormone releasing factor (LRF, pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) were synthesized. The ten agonistic analogues were [D-Lys6], [D-Orn6], [D-Lys6,des-Gly10,Pro9-NHEt], [D-Orn6,-des-Gly10,Pro9-NHEt]-LRF plus their respective lauric acid conjugates as well as [(Nepsilon-Ac)-D-Lys6] and [(Ndelta-Ac)-D-Orn6]-LRF. The eight antagonistic analogues were [des-His2,D-Lys6], [des-His2,D-Orn6], [des-His2,D-Lys6,des-Gly10,Pro9-NHEt], [des-His2,D-Orn6,des-Gly10,Pro9-NHEt]-LRF as well as their respective lauric acid conjugates. Biological activities of these analogues were determined in vitro, using LRF as the standard for the agonists and [des-His2,D-Ala6]-LRF for the antagonists. The potency of the agonists ranged from 1 to 17 times the activity of LRF while the antagonists had between 1 and 3 times the potency of [des-His2,D-Ala6]-LRF.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / chemical synthesis
  • Gonadotropin-Releasing Hormone / pharmacology
  • In Vitro Techniques
  • Luteinizing Hormone / metabolism
  • Pituitary Gland, Anterior / drug effects
  • Pituitary Gland, Anterior / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Gonadotropin-Releasing Hormone
  • Luteinizing Hormone