Novel anti-glycation therapeutic agents: glyoxalase I mimetics Sinan Battah, Naila Ahmed, Paul J. Thornalley * Department of Biological Sciences, University of Essex, Central Campus, Wivenhoe Park, Colchester, Essex CO4 3SQ, UK Abstract Glyoxalase I mimetic activity has been associated with the imidazole function. Histidine, histidine methyl ester and carnosine had glyoxalase I mimetic activity under physiological conditions. Carnosine scavenged methylglyoxal to form h-alanyl-N-DL-lactoyl-L-histidine (lactoyl- carnosine). This scavenging of a-oxoaldehydes by carnosine, and hydrolysis of the adduct formed to the corresponding aldonic acid catalysed by acyl-histidine hydrolase, represented a glyoxalase system mimetic activity. Glyoxalase mimetics are novel anti-glycation agents that may have therapeutic applications. Their specific activity, however, needs to be improved to have significant pharmacological effect. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Glyoxalase; Histidine; Carnosine; Methylglyoxal; Glycation 1. Introduction The glyoxalase system is the major physiological defence against highly reactive a- oxoaldehyde glycating agents, glyoxal, methylglyoxal and hydroxypyruvaldehyde. It consists of two enzymes, glyoxalase I and glyoxalase II, and a catalytic amount of GSH [1]. Glyoxalase I (EC 4.4.1.5) catalyses the formation of S-2-hydroxyacylglutathione from the hemithioacetal formed non-enzymatically from GSH and a-oxoaldehyde, RCOCHO + GSH RCOCH(OH)-SGWRCH(OH)CO-SG. Glyoxalase II (EC 3.2.1.6) cat- alyses the hydrolysis of S-2-hydroxyacylglutathione to the corresponding aldonic acid, 0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII:S0531-5131(02)00884-1 Abbreviations: GSH, glutathione. * Corresponding author. Tel./fax: +44-1206-873-010. E-mail address: thorp@essex.ac.uk (P.J. Thornalley). International Congress Series 1245 (2002) 107– 111