Read out Protease inhibitors are at the center of a special drug research project at the University of Würzburg. The researchers want to develop drugs that can be used in inflammatory diseases such as rheumatoid arthritis or pathologically increased muscle loss. To this end, the scientists are working on a specific class of protein-cleaving enzymes, the so-called cysteine ​​proteases and the associated cathepsins. They are involved in the development of many diseases. Among other things, they can also cause arthritis and muscle atrophy, heart attack, stroke and osteoporosis. Protease inhibitors are usually similar in structure. They have a reactive group that reacts with the active site of the enzymes, thereby blocking their function. The larger part of the molecules of the inhibitors is composed so that it can attach well to the proteases. In the design of protease inhibitors, peptides are usually used as lead structures today. However, these small protein molecules are not very suitable as drugs because they do not remain stable, especially in the gastrointestinal tract.

The Würzburg scientists now want to increase the stability of the inhibitors by replacing the peptides with peptide-like substances. This may also be possible to produce inhibitors that have a novel mechanism of action. To develop targeted inhibitors for individual cysteine ​​proteases, the researchers are trying to exploit the small differences in the surface structure (so-called substrate binding pockets) of the various proteases.

The substances that the scientists develop in their experiments can be tested immediately on the isolated proteases. This makes an immediate analysis of structure-activity relationships possible. In addition, experiments are planned on cell cultures (tests for cell toxicity) and on animals. The project is supported by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie and the Bundesforschungsministerium.

Drugs that hinder protein-cleaving enzymes in their work have proven themselves many times in the past: 20 years ago they presented a new concept for the treatment of hypertension. In 1996, they brought a decisive breakthrough in the treatment of AIDS. display



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