Pass me the protein stapler…

Scientists are developing short stretches of protein designed to fit into the surface of crucial molecules involved in cancer and arrest the disease...
07 October 2007


Last weekend Dr Kat was at the National Cancer Research Institute Conference in Birmingham, finding out about the latest advances in cancer science, and hobnobbing with some of the top researchers in the world.  One of the most interesting talks was from Professor Greg Verdine, from Harvard University, who highlighted an important "elephant in the room" when it comes to cancer research.

Nowadays, we have huge amounts of genetic and biological information about cancer, and scientists think that these could be targets for future cancer drugs. But around 80% of these are "undruggable" - they simply can't be hit with the types of drugs we currently have.  At the moment, we have small molecules. These include small chemical molecules which are probably only good at hitting about 10% of these targets, and biological molecules such as antibodies like Herceptin which can hit a further 10%.

So Verdine and his team are working on an entirely new type of drug - called synthetic biologicals, or stapled peptides. These are short stretches of protein designed to fit into the surface of crucial molecules involved in cancer.  Usually, such short peptides would wiggle and flap about all over the place, and not fit effectively into their target.  But Verdine has developed a way of "stapling" the two ends of the peptide together, using chemical bonds.  This fixes the shape of the peptide, meaning it can only wriggle in a limited way, so it fits into its target.

And the researchers have taken it a step further, designing peptides with multiple staples - which they call stitched peptides - that are even more stable. In fact, they can stand temperatures of up to 90 degrees C, and resist the powerful enzymes found in the stomach.  So this would make them good candidates for drugs to be given in a tablet form, which is ideal for a cancer drug.

So far, the researchers have been testing their stapled peptides in cancer cells grown in the lab, as well as animal models, and hope to go into clinical trials in humans in the near future.


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