The inhibition of methyltransferases is currently of high interest, particularly in the areas of microbial infection and cell proliferation, as there have been serious attempts to develop novel anti-microbial agents. In the present investigation, a series of 11 S-adenosyl-l-homocysteine analogues have been synthesized and effect of these analogues on DNA methylation catalyzed by DNA methyltransferases was studied. It was found that, while 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-d-ribofuranosyl)1,3-dideazaadenine was an activator of EcoP15I and HhaI DNA methyltransferases, 5'-S-(propionic acid)5'-deoxy-9-(1'-beta-dribofuranosyl)adenine inhibited the methyltransferases in a non-competitive manner. An understanding of the binding of analogues to DNA methyltransferases will greatly assist the design of novel anti-microbial compounds.