Modulating Protein-Prot ein Interactions via Peptide-Based Inhibitors
Biochemi st Canan Durukan demonstrates that many diseases, such as cancer, are caused by damaging interactions between proteins. To block these int eractions, drugs with a very carefully controlled form are required.< /strong>
Durakan's research focused on the discovery of inhibit ory molecules that disrupt protein-protein interactions involved in c ancer progression, with a particular focus on a target protein associ ated 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 s urfaces.
Using a structure-based drug design approach, she inve stigated 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 pep tide structure and conformational rigidity influence binding affinity , stability, and functional activity. In addition, she investigated h ow peptide structure influences enzymatic head-to-tail cyclization, a key method for generating engineered peptides with improved properti es.
More effective targeting
The motivation
for this research was to bridge fundamental peptide design principle
s and translational cancer research, with the goal of more effectivel
y targeting previously difficult-to-drug protein-protein interactions
.
The research demonstrates that many diseases, including cance r, are caused by damaging interactions between proteins, and that blo cking these interactions requires drugs with a very carefully control led shape. Durukan demonstrates that peptide-based molecules can be e ffective inhibitors of such interactions, but only when their size, f lexibility, and structure are properly balanced.
By studying pe ptide inhibitors targeting a protein complex involved in cancer, she discovered that shortening peptides can preserve their binding capaci ty while simultaneously making them easier to optimize. She also demo nstrated that making peptides more rigid - by chemically "locking" th eir shape - can improve their stability and activity, but that too mu ch rigidity can also alter their behavior in chemical reactions.
< p>One of the key conclusions is that successful drug development isn' t just about stronger molecules, but about carefully tuning their fle xibility. This insight will help in the development of better peptide -based drugs and materials.More information on the thesis< /a>
DESCRIPTION: 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 th e discovery of inhibitory molecules that disrupt protein-protein inte ractions involved in cancer progression, with a particular focus on a target protein associated with breast cancer. Protein-protein intera ctions play a central role in many oncogenic signaling pathways but a re difficult to target with conventional drugs due to their large and dynamic interaction surfaces. Using a structure-based drug design ap proach, she investigated peptide-based inhibitors as a strategy to se lectively block this interaction and ultimately support the developme nt of drug-like molecules. A key component of her work was studying h ow secondary peptide structure and conformational rigidity influence binding affinity, stability, and functional activity. In addition, sh e investigated how peptide structure influences enzymatic head-to-tai l cyclization, a key method for generating engineered peptides with i mproved properties. More effective targeting