在第2、6和10位进行修饰的促黄体生成激素释放因子类似物。

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

作者信息

Ling N C, Rivier J E, Monahan M W, Vale W W

出版信息

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.

摘要

合成了18种促黄体生成素释放因子（LRF，焦谷氨酸-组氨酸-色氨酸-丝氨酸-酪氨酸-甘氨酸-亮氨酸-精氨酸-脯氨酸-甘氨酸-氨基）类似物。10种激动剂类似物为[D-赖氨酸6]、[D-鸟氨酸6]、[D-赖氨酸6，去甘氨酸10，脯氨酸9-乙胺]、[D-鸟氨酸6，去甘氨酸10，脯氨酸9-乙胺]-LRF及其各自的月桂酸缀合物，以及[(Nε-乙酰基)-D-赖氨酸6]和[(Nδ-乙酰基)-D-鸟氨酸6]-LRF。8种拮抗剂类似物为[去组氨酸2，D-赖氨酸6]、[去组氨酸2，D-鸟氨酸6]、[去组氨酸2，D-赖氨酸6，去甘氨酸10，脯氨酸9-乙胺]、[去组氨酸2，D-鸟氨酸6，去甘氨酸10，脯氨酸9-乙胺]-LRF及其各自的月桂酸缀合物。以LRF为激动剂标准品，[去组氨酸2，D-丙氨酸6]-LRF为拮抗剂标准品，体外测定了这些类似物的生物活性。激动剂的效价为LRF活性的1至17倍，而拮抗剂的效价为[去组氨酸2，D-丙氨酸6]-LRF的1至3倍。