Two sides of drug discovery – characterizing a challenging target and exploring the potential of macrocyclic peptides.

Abstract

Target-driven drug discovery is a complex and multidisciplinary process that requires significant effort. It starts with identifying and validating a therapeutically relevant target. Once validated, producing this target in tractable form allows for detailed molecular structure analysis. This structural understanding is highly beneficial during subsequent drug discovery process, which involves screening for molecules that interact with the target while meeting certain therapeutic criteria. These molecules can be identified using a variety of screening techniques. Importantly, close collaboration between target structural characterisation and molecule screening techniques improves the overall efficiency of the drug discovery process. This thesis explores both key aspects: First, it will explore the discovery of macrocyclic peptide molecules by mRNA display that interact with targets while possessing therapeutically desirable properties. Second, it will explore efforts directed towards production and structural characterisation of a therapeutic target - the P2X7 receptor.