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

Abstract

Eighteen analogues of luteinizing hormone releasing factor (LRF, pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) were synthesized. The 10 agonistic analogues were [D-Lys6], [D-Lys6,des-Gly10,Pro9-NHEt], [D-Orn6,-des-Gly10,Pro9-NHEt]-LRF plus their respective lauric acid conjugates and (N.epsilon.-Ac)-D-Lys6] and [N.delta.-Ac)-D-Orn6]-LRF. The 8 antagonistic analogues were [des-His2,D-Lys6], [des-His2,D-Orn6], [des-His2,D-Lys6,des-Gly10,Pro9-NHEt], [des-His2,D-Lys6,des-Gly10,Pro9-NHEt]-LRF and 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 1-17 times the activity of LRF while the antagonists had between 1 and 3 times the potency of [des-His2,D-Ala6]-LRF in rats.