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

Nature has evolved thousands of enzymes to facilitate the myriad of chemical reactions which take place inside living organisms every dayThey accelerate, or ‘catalyse’, these reactions which would normally occur extremely slowly or not at all without enzymatic activity. Now, a study from researchers at Paris-Saclay University develops artificial enzymes anchored to the surface of living human cells.  The team state these enzymes could be used for therapeutic purposes, producing pharmacological compounds directly on the surface of specific cells, which could potentially reduce side effects. The study is published in the Journal of the American Chemical Society.

Metalloenzymes are a class of enzymes which contain a metal ion, such as zinc, iron or copper, which helps the enzyme speed up chemical reactions in the body.  Artificial metalloenzymes have been proven in catalysis, however, applications in living cells remain difficult as the metabolism of living cells damages metal ions, preventing the formation of enzymes.  The current study engineers an artificial enzyme which catalyzes a reaction used to synthesize drugs, agrochemicals and many other molecules, called the Diels-Alder reaction, right on the surfaces of living cells.

The current study uses a protein called the A2A adenosine receptor, which is naturally present on the surfaces of some cells in the body to develop their artificial enzyme. The lab modified a molecule that binds to this receptor with a copper-containing chemical group which catalyzes 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 that this enzyme catalyzes the Diels-Alder reaction with a yield of up to 50 percent.

The team state their discovery of 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 surmise they have designed artificial enzymes which sit on the surfaces of living cells and drive reactions no natural metalloenzyme, and no known human enzyme has been able to catalyze before.  For the future, the researchers state artificial enzymes might be designed that bind to proteins found only on specific cell types, for example, cancer cells. Then, the enzyme could convert an inactive compound into a drug to selectively kill those cells.

Source: American Chemical Society


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