Inhibition of glyoxalase I by S-substituted glutathiones

Abstract

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).

A trypanothione-dependent glyoxalase I with a prokaryotic ancestry in Leishmania major

“…S-p-bromobenzylglutathione was synthesized as described in ref. 22. All other reagents were standard commercial products of high purity.…”

Glutathione Transferase Omega 1 Catalyzes the Reduction of S-(Phenacyl)glutathiones to Acetophenones

“…1 H NMR spectra were recorded with a Brüker 400 MHz spectrometer; samples were dissolved in [ 2 H 6 ]DMSO, and chemical shifts are reported in ppm downfield from TMS. (Figure 2) were prepared by the method of Vince et al (20) by reaction of glutathione (Sigma) with 2-chloroacetophenone 1a (Fluka), 2,2′,4′-trichloroacetophenone 2a, 2-chloro-4′-fluoroacetophenone 3a, or 3-chloropropiophenone 4a (Aldrich). The precipitated products were washed extensively with ice-cold water to remove residual glutathione, dried, and stored at −20 °C.…”

Inhibition of glyoxalase I: a possible transition‐state analogue inhibitor approach to potential antineoplastic agents?

“…Sufficient glyoxalase I solution, in the presence of 0.1% bovine serum albumin (Sigma) as a stabilising agent 1201, was added to give an easily measured initial rate (fo~owed at 240 nm). Hemimercaptal substrate concentrations were calculated from the concentrations of GSH and methylglyoxal added, using a value of 3.1 X low3 M for the dissociation constant [9] of the hemimercaptal at pH 6.6. Data were analysed using an Exidy Sorcerer Minicomputer (Z80 chip); we are grateful to Mr John Torkington for programming assistance.…”