Enzyme chemistry of [formula omitted]hemiacetals: Synthesis and characterization of [formula omitted]mandeloylglutathione as an alternate substrate for glyoxalase I

Abstract

Both the D - and L -forms of S- dithio mandeloylglutathione (1) have been synthesized by a dithio ester-interchange reaction between GSH and S-carboxymethyl ( D , L )- dithio mandelate. Kinetic and product analysis studies indicate that yeast glyoxalase I efficiently catalyzes the stereoselective conversion of D -1 to GSH-phenylglyoxal dithio hemiacetal (2), isolated as a disulfide adduct between 2 and a second molecule of GSH. This observation suggests that dithio ester substrate analogues should be generally useful as mechanistic probes of enzyme catalyzed reactions involving thiohemiacetal intermediates.