转运RNA甲基转移酶抑制剂。S-腺苷锍盐。

Inhibitors of tRNA methyltransferases. S-Adenosylsulfonium salts.

作者信息

Gnegy M E, Lotspeich F J

出版信息

J Med Chem. 1976 Oct;19(10):1191-5. doi: 10.1021/jm00232a005.

DOI:10.1021/jm00232a005

Abstract

Three new compounds have been synthesized and tested as in vitro inhibitors of normal and tumor tRNA methyltransferases. These compounds are 5'-methylethyl(5'adenosyl) sulfonium chloride (MEAS), 5'-methylpropyl-(5'adenosyl)sulfonium chloride (MPAS), and 5'-ethylpropyl(5'-adenosyl)sulfonium chloride (EPAS) They were prepared by reacting an alkyl iodide with the appropriate alkyladenosyl thioether. Inhibition assays revealed all three compounds to be inhibitors of normal and tumor tRNA methyltransferases. The propyl compounds were slightly better inhibitors of the tumor tRNA methyl transferases. MPAS, EPAS, and MEAS had KI's of 58.5, 61.7, and 24.5, respectively, for the normal tRNA methyltransferases and 15.3, 13.8, and 44.3, respectively, for the tumor tRNA methyltransferases.

摘要

已合成三种新化合物，并作为正常和肿瘤tRNA甲基转移酶的体外抑制剂进行了测试。这些化合物是5'-甲基乙基（5'-腺苷基）氯化锍（MEAS）、5'-甲基丙基-（5'-腺苷基）氯化锍（MPAS）和5'-乙基丙基（5'-腺苷基）氯化锍（EPAS）。它们是通过使烷基碘与适当的烷基腺苷硫醚反应制备的。抑制试验表明，这三种化合物都是正常和肿瘤tRNA甲基转移酶的抑制剂。丙基化合物对肿瘤tRNA甲基转移酶的抑制作用略好。MPAS、EPAS和MEAS对正常tRNA甲基转移酶的KI值分别为58.5、61.7和24.5，对肿瘤tRNA甲基转移酶的KI值分别为15.3、13.8和44.3。

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