title: A new series of S-adenosyl-L-methionine synthetase inhibitors.
abstract: 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 these compounds was studied using recombinant rat liver S-adenosyl-L-methionine sythetase (alpha-isoform) fractionated from E. coli, transformed with the plasmid pSSRL-T7N. All the compounds tested were competitive 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 enzyme compared to those already reported for AdoMet synthetase from other mammalian tissues.
authors.affiliation: Laboratoire de chimie bioorganique, U.M.R. 6519 U.F.R. Sciences de Reims, France.
authors.forename: K
authors.initials: K
authors.lastname: Lavrador
authors.forename: B
authors.initials: B
authors.lastname: Allart
authors.forename: D
authors.initials: D
authors.lastname: Guillerm
authors.forename: G
authors.initials: G
authors.lastname: Guillerm
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004852:Epoxy Compounds / Q000494:pharmacology*; D006714:Homoserine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008716:Methionine Adenosyltransferase / Q000037:antagonists & inhibitors*; D051381:Rats
chemical_list: C116175:2-amino-4,5-epoxypentanoic acid; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; C037855:methoxine; D006714:Homoserine; D008715:Methionine; D008716:Methionine Adenosyltransferase