Small but beautiful- better pharmaceuticals through the displacement of water!

The tailor-made development of compounds that bind precisely to disease-relevant proteins is the high art of medicinal chemistry, with countless potential therapeutic applications such as treatment of depression, diabetes or viral infections. To avoid undesirable side effects, every atom counts! A reoccurring problem is the molecular manipulation of water molecules, which are ubiquitous in our cells.

In the most recent publication by Kolos and Pomplun et. al. in the renowned journal Chemical Science, the Prof. Felix Hausch lab could show that the strategically positioning of a single methyl group can displace a water molecule in FK506-binding proteins, resulting in a 10-fold increase in activity. This led to the most effective compounds for FK506-binding proteins known to date. With these substances, it was possible to inhibit signaling pathways in cells that are important for cancers such as myeloma or for hematological diseases. These compounds and the associated findings enable scientists at the TU Darmstadt as well as medicinal chemist worldwide to further advance the development of therapies for FKBP-associated diseases.