ABSTRACT
Several other AdoMet analogs that do not support enzymatic reactions but can func tion as inhibitors are shown in Table 2. The natural product S-adenosyl-L-homocysteine (AdoHcy or SAH, 11) is formed after methyl group transfer and is a potent product inhibitor of MTases.17 The sulfoxide and sulfone analogs 1217'19 and 1319 show only moderate inhibitory effects on AdoMet-dependent enzymes but they were found to bind with good affinities to an AdoMet-binding riboswitch.20 In contrast to aziridine cofactor 9 and nitrogen mustard 10 the nitrogen analogs 142122 and 1523 are not converted by MTases. The nitrogen analog 14 has an unusual low pKz value around 7.1 and acts as a charge-switchable nonreactive AdoMet mimic.24 The natural product sinefungin 1625 and its close analog dehydrosinefungin 17 can be regarded as transition state analogs for MTases and are very potent competitive inhibitors. In addition, sinefungin 16 has antiviral, antifungal and antiparasidic activities but due to a lack of specificity it also shows high in vivo toxicity which strongly limits its clinical use.26 Finally, the vinyl analog 1827 has been postulated to act as an irreversible enzyme inhibitor in vivo and in vitro.28
