Expanding the toolbox of protein-templated reactions for early drug discovery

Despite recent developments in technology and techniques in today’s drug discovery, accessing new bioactive compounds is still challenging. It is of utmost importance both for medicinal chemists as well as pharmaceutical companies to accelerate this lengthy trajectory. In this thesis, we aimed to establish novel strategies to facilitate faster and more efficient hit identification, the early stage of the drug-discovery process. In order to achieve this goal, we used target-guided synthesis (TGS) in which the biological target, in our case a protein, templates the formation of its own inhibitors from a pool of complementary building blocks. This efficient technique accelerates the drug-discovery process, namely hit-identification/optimization, enabling the selection of the best binders without prior synthesis, purification and biochemical evaluation of each individual compound.