Modulating Protein-Protein Interactions via Peptide-Based Inhibitors
Biochemist Canan Durukan demonstrates that many diseases, such as cancer, are caused by damaging interactions between proteins. To block these interactions, drugs with a very carefully controlled form are required.
Durakan's research focused on the discovery of inhibitory molecules that disrupt protein-protein interactions involved in cancer progression, with a particular focus on a target protein associated with breast cancer. Protein-protein interactions play a central role in many oncogenic signaling pathways but are difficult to target with conventional drugs due to their large and dynamic interaction surfaces.
Using a structure-based drug design approach, she investigated peptide-based inhibitors as a strategy to selectively block this interaction and ultimately support the development of drug-like molecules. A key component of her work was studying how secondary peptide structure and conformational rigidity influence binding affinity, stability, and functional activity. In addition, she investigated how peptide structure influences enzymatic head-to-tail cyclization, a key method for generating engineered peptides with improved properties.
More effective targeting
The motivation for this research was to bridge fundamental peptide design principles and translational cancer research, with the goal of more effectively targeting previously difficult-to-drug protein-protein interactions.
The research demonstrates that many diseases, including cancer, are caused by damaging interactions between proteins, and that blocking these interactions requires drugs with a very carefully controlled shape. Durukan demonstrates that peptide-based molecules can be effective inhibitors of such interactions, but only when their size, flexibility, and structure are properly balanced.
By studying peptide inhibitors targeting a protein complex involved in cancer, she discovered that shortening peptides can preserve their binding capacity while simultaneously making them easier to optimize. She also demonstrated that making peptides more rigid - by chemically "locking" their shape - can improve their stability and activity, but that too much rigidity can also alter their behavior in chemical reactions.
One of the key conclusions is that successful drug development isn't just about stronger molecules, but about carefully tuning their flexibility. This insight will help in the development of better peptide-based drugs and materials.
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