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Fast synthesis could boost drug development
Date:3/18/2014

IT team adapted the synthesis reactions so they can be done in a continuous flow system. Using this approach, each amino acid addition takes only a few minutes, and an entire peptide can be assembled in little more than an hour.

In future versions, "we think we're going to be able to do each step in under 30 seconds," says Pentelute, who is also an associate member of the Broad Institute. "What that means is you're really going to be able to do anything you want in short periods of time."

The new system has storage vessels for each of the 20 naturally occurring amino acids, connected to pumps that pull out the correct one. As the amino acids flow toward the chamber where the reaction takes place, they travel through a coil where they are preheated to 60 degrees Celsius, which helps speed up the synthesis reaction.

This system produces peptides as pure as those produced with existing machines. "We're on par with the world's best state-of-the-art synthesis, but we can do it much faster now," Pentelute says.

With this technology, scientists could design and rapidly test new peptides to treat cancer and other diseases, as well as more effective variants of existing peptides, such as insulin, Pentelute says. Another benefit of this high-speed approach is that any potential problems with a particular peptide synthesis can be detected much sooner, allowing the researchers to try to fix it right away.

Another area Pentelute plans to pursue is creating so-called "mirror-image" proteins. Nearly all proteins that exist in nature are made of L amino acids, whose structures have a right-handed orientation. Creating and studying peptides that are mirror images of these natural proteins could pave the way to developing such peptides as new drugs with completely different functions from the right-handed versions.

Technology with an impact

In a separate paper published in the same issue of ChemBioChem, the
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Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

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