促黄体生成素释放激素的构效关系

Structure-activity relationships in luteinizing hormone-releasing hormone.

作者信息

Prasad K U, Roeske R W, Weitl F L, Vilchez-Martinez J A, Schally A V

出版信息

J Med Chem. 1976 Apr;19(4):492-5. doi: 10.1021/jm00226a008.

Abstract

Three analogs of luteinizing hormone-releasing hormone (LH-RH) of the structure less than Glu-His-Trp-Ser-Tyr-Gly-Gly-Leu-Arg-Pro-Gly-NH2, involving substitutions inpositions 1, 3, and 8 with nonprotein amino acids, have been synthesized by the solid-phase method. They are [pyro-L-alpha-(1-aminoadipic)]-LH-RH, [3-(2-naphthyl)-L-Ala3]-LH-RH, and [delta-N-i-Pr-L-Orn8]-LH-RH. Their LH-RH activities in vivo were 12.5, 51.8, and 3.7% that of LH-RH, respectively, in the assay using ovariectomized, estrogen- and progesterone-treated rats. In a test based upon subcutaneous injection into immature male rats, [3-(2-naphthyl)-Ala3]-LH-RH released 1.2 times as much LH and 0.8 times as much FSH as synthetic LH-RH.

摘要

通过固相法合成了三种结构小于谷氨酸-组氨酸-色氨酸-丝氨酸-酪氨酸-甘氨酸-甘氨酸-亮氨酸-精氨酸-脯氨酸-甘氨酸-氨基的促黄体生成激素释放激素（LH-RH）类似物，它们在第1、3和8位被非蛋白质氨基酸取代。它们分别是[焦-L-α-(1-氨基己二酸)]-LH-RH、[3-(2-萘基)-L-丙氨酸3]-LH-RH和[δ-N-异丙基-L-鸟氨酸8]-LH-RH。在使用去卵巢、雌激素和孕酮处理的大鼠进行的试验中，它们在体内的LH-RH活性分别为LH-RH的12.5%、51.8%和3.7%。在一项基于皮下注射给未成熟雄性大鼠的试验中，[3-(2-萘基)-丙氨酸3]-LH-RH释放的LH量是合成LH-RH的1.2倍，FSH量是合成LH-RH的0.8倍。