Inhibitors of tRNA methyltransferases. S-Adenosylsulfonium salts.

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.