Analogues of luteinizing hormone releasing factor modified at positions 2, 6, and 10.
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.
D000818:Animals; D002478:Cells, Cultured; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D007987:Gonadotropin-Releasing Hormone; D007986:Luteinizing Hormone