A novel technology for streamlined synthesis, screening, and sequencing of privileged cyclic peptide scaffolds (2011)


Human Health


Over the past several years there has been increasing interest in drugs that are peptides and proteins. The reason that peptides and proteins appear promising is that they are made of amino acids, which humans naturally have, and are therefore less likely to cause unwanted side effects. Peptides control a vast range of processes in human cells. The vast majority of peptides are linear: they are built of amino acid building blocks into longer molecules that are flexible akin to spaghetti. Despite the biological significance of these flexible molecules, they are not good as therapeutic agents because our bodies have found a way to rapidly degrade them back into the amino acid constituents. If one could “tie up the loose ends” and create a circular peptide molecule out of a linear one, it may still have the desired biological effect. However, the stability is expected to be drastically increased because the body does not know how to chop circular molecules as efficiently as their linear counterparts.

One may, therefore, ask a question: “why don’t we see more circular peptides as drugs on the market?” The answer lies in extreme technical difficulties in making these circular molecules out of linear ones. In 2010, Dr. Andrei Yudin and his students at the University of Toronto found that the molecules of cyclic peptides can be readily made using novel chemistry developed in the Yudin lab. Funded in part by OGI (SPARK), the Yudin lab has made an exciting discovery that not only the stability but also the ability to enter human cells is increased when circular molecules are made with their method. With this important finding in hand, the Yudin lab is extremely excited about asking the next logical question: “now that your molecules can enter human cells, can they also kill disease-associated proteins found in infected cells?”. The SPARK grant has enabled us to build a much needed momentum that has resulted in several other grants, most notably – CQDM. Additionally, the Yudin group has initiated a collaboration with Eric Marsault (Department of Pharmacology, University of Sherbrooke). The stage is now set for an exciting path towards real therapeutics. For more information, please click here.