A NEW SERIES OF S-ADENOSYL-L-METHIONINE SYNTHETASE INHIBITORS

A new series of epithio and epoxy amino acid analogues of L-methionine or L-methoxinine were examined as potential inhibitors of the enzyme S-adenosylmethionine (AdoMet) synthetase. The kinetic behaviour of the se compounds was studied using recombinant rat liver S-adenosyl-L-meth ionine sythetase (alpha-isoform) fractionated from E. coli, transforme d with the plasmid pSSRL-T7N. All the compounds tested were competitiv e inhibitors with respect to L-methionine and the (2S, 4S)-2-amino-4,5 -epoxy pentanoic acid was found to be a very potent inhibitor of the e nzyme compared to those already reported for AdoMet synthetase from ot her mammalian tissues.