Researchers develop an artificial enzyme that speeds reactions in living cells.

In the course of evolution, nature has produced thousands of enzymes to facilitate the myriad of chemical reactions taking place inside living organisms every day.  Enzymes are responsible for accelerating or catalyzing reactions in the body that would normally occur extremely slowly or not at all without them. Now, a study from researchers at Paris-Saclay University develops artificial enzymes anchored to the surface of living human cells.  The team states these enzymes could be used for therapeutic purposes, producing pharmacological compounds directly on the surface of specific cells, potentially reducing side effects. The study is published in the Journal of the American Chemical Society.

Previous studies show metalloenzymes are a class of enzyme-containing a metal ion, such as zinc, iron, or copper, to speed up chemical reactions in the body.  Artificial metalloenzymes have been proven in catalysis, however, applications in living cells remain difficult as metabolism by its very nature damages metal ions, preventing the formation of enzymes.  The current study engineers an artificial enzyme capable of catalyzing the Diels-Alder reaction right on the surfaces of living cells. This reaction is used to synthesize drugs, agrochemicals, and many other molecules.

The current study uses a protein called the A2A adenosine receptor, naturally present on the surfaces of some cells in the body, to develop their artificial enzyme. The lab modified a molecule known to bind to this receptor with a copper-containing chemical group for catalyzing the Diels-Alder reaction. Results show the compound attaches to the A2A adenosine receptors on living human cells in vitro, forming an artificial enzyme. Data findings show this enzyme catalyzes the Diels-Alder reaction with a yield of up to fifty percent.

The team states their discovery showing the potential of artificial metalloenzymes associating metal complexes with membrane receptors is a big step forward for in vivo catalysis.  They go on to add these artificial enzymes could be used for the synthesis of either drugs or deficient metabolites, and for the activation of prodrugs, leading to therapeutic tools with unforeseen applications.

The team surmises they have designed artificial enzymes able to sit on the surfaces of living cells and drive reactions no known human enzyme has been able to catalyze before.  For the future, the researchers state artificial enzymes might be designed to bind proteins found only on specific cell types, for example, cancer cells, with the artificial enzyme converting innocuous chemicals into drugs to kill the foreign invader.

Source: American Chemical Society

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