Scientists around the world are currently researching vaccines and medicines to combat the coronavirus, which is infecting more and more people at breakneck speed. Researchers at the Technical University of Munich (TUM) have now developed a novel method that could come closer to a remedy for the SARS-CoV-2 virus.
The researchers have developed a protein reagent that can recognize biological cell structures and block the spread of a disease in the body when it attaches to the sugar structures of a cell or a pathogen. Background: The viruses that enter the organism during infection and multiply in the body cells often target the sugar structures of their host cells. Or they have characteristic sugar structures even on their surface.
“The detection of special sugar molecules, so-called carbohydrates, is of crucial importance in many biological processes,” explains Arne Skerra, professor of biological chemistry. Current research results from his laboratory would now enable the development of novel binding proteins for biological sugar structures that play a major role in both cancer and infectious diseases.
A body has to recognize which cells belong where and whether they belong in the body or not. Therefore, these cells often have a sugar chain marker on the outside of the cell membrane or on membrane proteins. Pathogens have their own sugar structure or can stick to one. In contrast, proteins generally have little affinity for sugars, making them difficult to recognize.
The reason for this is that water and sugar molecules look very similar and are practically camouflaged in the aqueous environment of the cells. Prof. Skerra and his team were therefore looking for an artificial binding protein with a chemical grouping that makes it easier to recognize the biological sugar structures.
Prof. Arne Skerra (right) and his team Dr. Andreas Eichinger and Carina A. Sommer in the laboratory. © TUM Chair for Biological Chemistry
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New class of binding proteins for sugar molecules
Proteins found in nature consist of a selection of a total of amino acids. However, the researchers also used an artificial amino acid “with the means of synthetic biology”, reports researcher Carina A. Sommer. “We have successfully integrated a boric acid group that has an inherent affinity for sugar molecules into the amino acid chain of a protein. We have created a fundamental new class of binding proteins for sugar molecules.
This artificial sugar binding function is said to be superior to natural binding proteins (so-called lectins) both in their strength and in the possibilities for specific design. “The sugar binding activity of boric acid and its derivatives has been known for almost a century,” says Prof. Skerra. Boric acid is widespread in inanimate nature and hardly toxic, but organisms have so far practically not used it. “With the help of X-ray structure analysis, we managed to elucidate the crystal structure of a model complex of this artificial protein and were thus able to confirm our biomolecular concept,” explains her colleague Dr. Andreas Eichinger.
Further research for medical applications
After about five years of basic research, the development can now be used for specific medical applications, emphasizes Prof. Skerra. “Our findings should not only support the future development of new carbohydrate ligands in biological chemistry, but also pave the way for high-affinity active ingredients to control or block medically relevant sugar structures on cell surfaces.
For example, the “blocking agent” could be used in oncology or virology, in which strong cell growth or the docking of pathogens with cells plays a role. Blocking the sugar-binding function could slow down the disease and give the immune system more time to fight the disease.
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