Further stereochemical studies on methyl transfer reactions

Abstract

At the last Transmethylation Conference we presented a preliminary account of studies aimed at determining the steric course of the transfer of a methyl group from methionine or S-adenosylmethionine (AdoMet) to various C-, N-, or O-atoms in biological molecules catalyzed by methyltransferase enzymes, and we now wish to summarize the results obtained to date. Pursuit of this goal required the use of methyl groups made chiral by virtue of the presence of the three isotopes of hydrogen, H, D and T (for a review see Floss and Tsai, 1979), and it involved the following tasks: 1) Synthesis of methionine and AdoMet carrying a chiral methyl group of known configuration. 2) Enzymatic transfer of the methyl group to the substrate. 3) Degradation of the product to carve out the chiral methyl group and convert it into a compound suitable for configurational analysis, using only stereospecific reactions of known steric course. 4) Configurational analysis of the methyl group.