Theodore Flack

Selective Helix-Mimetics as Tools for Malaria Research

Theodore Flack - Writing up


Protein-protein interactions (PPIs) participate in all cellular processes, including those involved in the development of disease. As such, improving our understanding into these interactions is of significant interest. Around 62% of PPIs have an alpha-helical motif present at the interface, and so mimicry of this secondary structure represents an effective method for perturbing these binding events.
One such sub-group of helix-mediated PPIs are those which occur between a major class of molecular motor protein, myosins, and their regulatory proteins, which are critical for the effective functioning of the motors. Myosin A (Myo A) and myosin tail interacting protein (MTIP) associate with one another as part of the mechanism used by malaria parasites to invade host red blood cells. The project aims to design and synthesise a series of inhibitors of this PPI and test their activity in both biophysical assays and in live parasites. This will enable us to develop a robust method for future investigations into the role of motor proteins in other areas of biology.