Studies on the Inhibition of Glyoxalase I by S-Substituted Glutathiones

S-Substituted glutathiones were prepared and investigated as inhibitors of the enzyme, glyoxalase I. A nonpolar region exists on the enzyme and plays an important role in the formation of an enzyme-inhibitor complex. The amount of inhibition of glyoxalase increases as the alkyl chain is lengthened from methyl to n-octyl. Several S-arylglutathiones were also prepared in order to take advantage of this nonpolar region on the enzyme. For example, S-(p-bromobenzyl)glutathione (14) gave about 920-fold better binding than the previously reported S-methylglutathione (1).