Macrocyclic peptides as chemical probes for protein-protein interactions

Peptides control a vast range of intra- and intercellular processes. However, linear peptides suffer from instability and poor cell permeability, which limits their application as therapeutic agents. In contrast to linear peptides, cyclic variants are more resistant to both exo- and endoproteases, which explains the therapeutic potential of this class of molecules. Peptide macrocycles have shown remarkable capacity for functional fine-tuning.

Analysis of cell signaling in cancer has identified a plethora of signaling pathways that are implicated in cancer initiation and progression. Some signaling systems are characterized by enrichment in specific modular domain classes. Because these domains bind short peptides, it should be possible to design specific macrocyles that would present the corresponding amino acid sequences in a conformationally biased form. This strategy would provide an effective means of developing potential cancer therapeutics.

Vishal Rai
Faculty Supervisor: 
Dr. Andrei Yudin