Modulating Protein-P rotein Interactions via Peptide-Based Inhibitors
B iochemist Canan Durukan demonstrates that many diseases, such as canc er, are caused by damaging interactions between proteins. To block th ese interactions, drugs with a very carefully controlled form are req uired.
Durakan's research focused on the discovery of inhibitory molecules that disrupt protein-protein interactions involv ed in cancer progression, with a particular focus on a target protein associated with breast cancer. Protein-protein interactions play a c entral role in many oncogenic signaling pathways but are difficult to target with conventional drugs due to their large and dynamic intera ction surfaces.
Using a structure-based drug design approach, s he investigated peptide-based inhibitors as a strategy to selectively block this interaction and ultimately support the development of dru g-like molecules. A key component of her work was studying how second ary peptide structure and conformational rigidity influence binding a ffinity, stability, and functional activity. In addition, she investi gated how peptide structure influences enzymatic head-to-tail cycliza tion, a key method for generating engineered peptides with improved p roperties.
More effective targeting
The mot
ivation for this research was to bridge fundamental peptide design pr
inciples and translational cancer research, with the goal of more eff
ectively targeting previously difficult-to-drug protein-protein inter
actions.
The research demonstrates that many diseases, includin g cancer, are caused by damaging interactions between proteins, and t hat blocking these interactions requires drugs with a very carefully controlled shape. Durukan demonstrates that peptide-based molecules c an be effective inhibitors of such interactions, but only when their size, flexibility, and structure are properly balanced.
By stud ying peptide inhibitors targeting a protein complex involved in cance r, she discovered that shortening peptides can preserve their binding capacity while simultaneously making them easier to optimize. She al so demonstrated that making peptides more rigid - by chemically "lock ing" their shape - can improve their stability and activity, but that too much rigidity can also alter their behavior in chemical reaction s.
One of the key conclusions is that successful drug developme nt isn't just about stronger molecules, but about carefully tuning th eir flexibility. This insight will help in the development of better peptide-based drugs and materials.
More information on the thesis
DESCRIPTION: Modulating Protein-Protein Interactions via Peptide-Based Inhibitors Biochemist Canan Durukan demonstrates that many d iseases, such as cancer, are caused by damaging interactions between proteins. To block these interactions, drugs with a very carefully co ntrolled form are required.Durakan's research focused on the discovery of inhibitory molecules that disrupt protein-protein inter actions involved in cancer progression, with a particular focus on a target protein associated with breast cancer. Protein-protein interac tions play a central role in many oncogenic signaling pathways but ar e difficult to target with conventional drugs due to their large and dynamic interaction surfaces.Using a structure-based drug design appr oach, she investigated peptide-based inhibitors as a strategy to sele ctively 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 bi nding 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 imp roved properties.More effective targeting