Enzymes are important targets in drug research to fight against pathogens and the body’s own disorders that lead to diseases states. At first, it seems that proteases do not belong to this group of enzymes, because they are only involved in protein turnover, which is completely wrong. One group of proteases; cysteine proteases, which are preferentially found in the lysosome, are also involved in many other cellular processes than just normal degradation of extracellular material and antigen processing. One of these enzymes is cathepsin L., which is involeved, among other things, in the development of severe acute respiratory syndrome (SARS). In the last decades, cysteine cathepsins have also become an interesting topic for studying the inhibitory effect.
One of the most studied zinc complexes is zinc pyrithione, which has been long known for its antimicrobial properties and it is a key component in commercially available anti-dandruff shampoos. Beside antifungal activity, zinc pyrithione exhibits antiviral activity, making it a potential drug against viruses. Little is known about its effect on cathepsin L, but on the other hand, zinc ions are known to inhibit cathepsin B, which also belongs to CA1 family of papain-like proteases.
For this reason, we have decided to examine the effect of pyrithione in combination with zinc salts on the cathepsin L activity. We first determined the stability of all tested components by UV/VIS spectroscopy. After that, we performed enzyme test, where the fluorescence intensity was measured using a fluorogenic substrate. From the obtained data, we determined the EC50 values of the tested components and found out that the inhibitory effect of zinc salts increases with the addition of pyrithione. Such knowledge is especially useful in designing an experiments, that would speed up the search for potential enzyme inhibitors.
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