Using photoaffinity probes based on a motif found in kinase-targeting anticancer drugs, researchers from KU Leuven have shown that their off-targets are not only found in the kinase families, but also in other proteins. They have published their findings in Communications Chemistry.

A common way to study enzymes is to use activity-based probes. These small molecules contain a reactive moiety that mimics the substrate of an enzyme. Depending on the probe, you can form a covalent bond between it and the enzyme. If you attach a molecular label to the probe, you can then filter out the enzyme for analysis.

‘But sometimes there are enzymatic mechanisms for which mechanism-based inhibitors do not apply’, says Steven Verhelst, professor of chemical biology at KU Leuven. In this case, photoaffinity-based probes could be used. ‘These get around the problem by binding non-covalently to the enzyme. A few years ago, our group started to look at various targets, including kinases.’