MIT chemists devise new way to manufacture peptides
Speeding up the process to just a few hours
Small protein fragments, also called peptides, are promising as drugs because they can be designed for very specific functions inside living cells.
Insulin and the HIV drug Fuzeon are some of the earliest successful examples, and peptide drugs are expected to become a US$25bn market by 2018.
But manufacturing peptides takes several weeks, making it difficult to obtain large quantities and rapidly test their effectiveness and this has prevented peptide drugs from reaching their full potential.
Now a team at the Massachusetts Institute of Technology (MIT) in the US has designed a way to manufacture peptides in just a few hours. The new system, described in 21 March issue of the journal ChemBioChem, could have a major impact on peptide drug development, says Bradley Pentelute, an assistant professor of chemistry and leader of the research team.
'Peptides are ubiquitous. They’re used in therapeutics, they’re found in hydrogels, and they’re used to control drug delivery. They’re also used as biological probes to image cancer and to study processes inside cells,' says Pentelute. 'Because you can get these really fast now, you can start to do things you couldn’t do before.'
Because you can get these peptides really fast now, you can start to do things you couldn’t do before
Therapeutic peptides usually consist of a chain of 30 to 40 amino acids, the building blocks of proteins. Many universities, including MIT, have facilities to manufacture these peptides, but the process usually takes two to six weeks, using machines developed about 20 years ago.
These machines require about an hour to perform the chemical reactions needed to add one amino acid to a chain. To speed up the process, the MIT team adapted the synthesis reactions so that 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, Pentelute thinks they will be able to do each step in under 30 seconds.
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 60ºC, which helps speed up the synthesis reaction.
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. Another benefit of this high-speed approach is that any potential problems with a particular peptide synthesis can be detected much sooner, allowing it to be fixed straightaway.
Pentelute also plans to create 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.
In a separate paper published in the same issue of ChemBioChem, the researchers demonstrated that they could use this technology not only to synthesise peptides, but also to combine them to form large synthetic proteins. To demonstrate the technology, they created an antibody mimic that has 130 amino acids, as well as a 113-amino-acid enzyme produced by bacteria.
