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 ¦Á-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 ¦Á-hydroxy thioesters. This reaction is exceptionally enantioselective and the ¦Á-hydroxythioester products are of high value for multiple synthetic applications. The applicability was highlighted by the coupling reagent-free synthesis of several optically pure ¦Á-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 4th, with the title of ¡°Biomimetic Catalytic Transformation of Toxic ¦Á-Oxoaldehydes to High-Value Chiral ¦Á-Hydroxythioesters using Artificial Glyoxalase I¡±.
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