促黄体生成素释放激素和促甲状腺激素释放激素的2-L-β-（吡唑基-1）丙氨酸类似物的合成及其生物学性质

Synthesis and biological properties of the 2-L-beta-(pyrazolyl-1)alanine analogs of luteinizing hormone-releasing hormone and thyrotropin-releasing hormone.

作者信息

Coy D H, Hirotsu Y, Redding T W, Coy E J, Schally A V

出版信息

J Med Chem. 1975 Sep;18(9):948-9. doi: 10.1021/jm00243a018.

Abstract

The luteinizing hormone-releasing hormone (LH-RH) analog, less thanGlu-Pyr(1)Ala-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2, and the thyrotropin-releasing hormone (TRH) analog, less thanGlu-Pyr(1)Ala-Pro-NH2, were synthesized by azide couplings of the dipeptide hydrazide, less thanGlu-Pyr(1)Ala-NHNH2, to the C-terminal octapeptide of LH-RH and to proline amide, respectively. In an ovariectomized, steroid-blocked rat assay, the LH-RH analog was found to have only 1% of the LH-releasing activity of the natural hormone. The TRH analog was 1.5 times more effective than TRH itself in releasing TSH in vivo from the anterior pituitary of mice. This peptide is one of two synthetic peptides so far discovered which are more potent than TRH.

摘要

促黄体生成激素释放激素（LH - RH）类似物，小于Glu - Pyr(1)Ala - Trp - Ser - Tyr - Gly - Leu - Arg - Pro - Gly - NH2，以及促甲状腺激素释放激素（TRH）类似物，小于Glu - Pyr(1)Ala - Pro - NH2，分别通过二肽酰肼小于Glu - Pyr(1)Ala - NHNH2与LH - RH的C末端八肽和脯氨酸酰胺的叠氮偶联反应合成。在去卵巢、类固醇阻断的大鼠实验中，发现LH - RH类似物的促黄体生成素释放活性仅为天然激素的1%。TRH类似物在体内从小鼠垂体前叶释放促甲状腺激素方面比TRH本身有效1.5倍。这种肽是迄今为止发现的两种比TRH更有效的合成肽之一。