A research team led by Prof. Choong Eui SONG (Dept. of Chemistry) has developed a new catalyst system motivated by the detoxification process within the body.

Nature has evolved a wealth of proteins called enzymes that catalyse the chemical reactions necessary to sustain all life on Earth. Glyoxalases (I and II) and glutathione constitute a set of glyoxalase enzymes which carry out the detoxification of methylglyoxal and other reactive α-keto aldehydes, by the sequential action of two thiol-dependent enzymes.

Hereby, the research team developed an artificial glyoxalase I that successfully catalyses the enantioselective isomerization of the spontaneously formed hemithioacetal adducts between diverse 2-oxoaldehydes and thiols, as GSH surrogates into chiral α-hydroxy thioesters. This reaction is exceptionally enantioselective and the α-hydroxythioester products are of high value for multiple synthetic applications. The applicability was highlighted by the coupling reagent-free synthesis of several optically pure α-hydroxyamides, highly important drug candidates in the pharmaceutical industry. Similar to real enzymes, the enforced proximity of the catalyst and substrates by a chiral cage in situ formed by the incorporation of potassium salt can enhance reactivity and efficiently transfer the stereochemical information.

Prof. SONG said “our strategy will provide new scientific insights for developing an artificial enzyme which can outperform the original enzyme. Furthermore, this work would also provide a potential starting point for developing artificial enzymes which might be used for pharmaceutical areas.”

This research was published in the Nature Communications as of April 4^th, with the title of “Biomimetic Catalytic Transformation of Toxic α-Oxoaldehydes to High-Value Chiral α-Hydroxythioesters using Artificial Glyoxalase I”.