Researchers are working on markers for faster detection of diseases

"Our markers will be used, for example, in diagnostic tests that will enable faster detection of a given disease" - says the project leader, Prof. Marcin Drąg from the Faculty of Chemistry, Wrocław University of Science and Technology.

Proteolytic enzymes (proteases, peptidases) are a group of enzymes that cleave peptide bonds and break down proteins into simpler components - peptides and amino acids. According to Prof. Drąg, in humans proteases constitute a group of about 700 enzymes identified to date. "They are responsible for controlling all metabolic pathways, that is, they practically control everything that leads to the fact that our body is able to live, survive and function normally" - emphasises the scientist.

Their incorrect functioning leads to the emergence of disease states in the body. "The problem occurs when these enzymes escape control, cease to function normally and start to be involved in many pathogenic processes. Virtually all civilization diseases are largely linked to incorrect function of proteolytic enzymes" - he adds.

These diseases include all types of cancers (in every type of cancer there are incorrectly functioning protases), diabetes (in which some of the most effective drugs today affect proteases), as well as neurodegenerative diseases and bacterial and viral infections.

"For example, key enzymes in the detection and imaging of cancers are proteases from the cathepsin family, whereas in the case of metastasis, matrix metalloproteinases MMP-2 and MMP-9 play a very important role. Another important enzyme class involved in neoplastic processes are deubiquitinating enzymes" - adds the scientist.

As part of their project, Wrocław scientists want to create highly sensitive markers for imaging individual proteolytic enzymes/ These markers should be extremely selective with regard to a specific enzyme, not the entire group.

Researchers want to detect the activity of a single enzyme. "This is important because very often the enzyme belongs to the family of proteases, but it is the only enzyme that participates in the development of the disease. We want to follow its functions only, and not the functions of other enzymes" - notes Prof. Drąg.

In his opinion, there are currently no tools that would practically allow to perform these operations, because there are only a few classes of compounds that are close but have no practical applications. "We will try to create markers that will be specific exclusively to the given enzyme" - he adds.

According to Prof. Drąg, the markers can be used in medicine primarily for diagnostic tests, for quick detection of a given disease. "When a given protease is secreted into the blood, we often do not know that a given disease is developing, because it is at a very early stage. Our markers will tell that something bad is happening in the body" - explains Prof. Drąg.

Wrocław scientists want to develop markers containing fluorescent groups that will "highlight" diseased cells. According to Prof. Drąg, they could also have practical applications in cancer surgeries.

"These markers will allow to tag cancer cells, which can be used in surgery for selective removal of tumours. We will be able to +highlight+ cancer cells only, and the surgeon will be able to selectively cut them" - emphasises the scientist.

The project aiming to create a technology for designing selective markers for imaging proteolytic enzymes is scheduled for three years, but studies on markers will probably take much longer. "But we think that the foundations that require the creation of entire technology will be completed in three years" - concludes the researcher.

In the years 2005-2008, Prof. Marcin Drąg worked at The Burnham Institute for Medical Research in California. After returning, he began independent research in the field of biological chemistry and combinatorial chemistry, using unnatural amino acids in the study of proteolytic enzymes. The researcher is a laureate of the START and FOCUS programmes, and now the TEAM programme of the Foundation for Polish Science, and the Harmonia and Opus competitions organized by the National Science Centre.

The research project "Challenges in the design of selective activity-based probes for proteolytic enzymes" received PLN 3.5 million funding from the TEAM programme of the Foundation for Polish Science.

PAP - Science in Poland, Kamil Szubański

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