A peptide in an hour
Rapid synthesis of peptides will accelerate the development of drugs
NanoNewsNet based on MIT materials: Fast synthesis could boost drug development
Small proteins and their fragments – oligopeptides – are promising as medicines, since they are able to perform various narrowly targeted functions inside living cells. Insulin and the drug Fuseon used to treat AIDS are among the earliest successful examples of peptide drugs, and their market is expected to reach $25 billion by 2018.
However, the full realization of the potential of this group of drugs is hindered mainly by the speed of peptide synthesis: their production takes several weeks, which makes it difficult to obtain them in large quantities and quickly check their effectiveness.
Now this bottleneck may soon disappear: a group of chemists and chemical engineers from the Massachusetts Institute of Technology (MIT) has developed a way to produce peptides in a matter of hours. According to the head of the research group, Associate professor of Chemistry at MIT Bradley Pentelute, the new system described in a recent issue of the journal ChemBioChem (Rapid Flow-Based Peptide Synthesis) can have a significant impact on the development of peptide drugs.
"Peptides are ubiquitous. They are used in therapy, they are present in hydrogels and are used to control drug delivery. In addition, they are used as biological probes to visualize cancer and study intracellular processes," explains Professor Pentelut. "Since they can now be obtained very quickly, we will be able to start doing things that we could not do before."
Therapeutic peptides are usually chains of 30-40 amino acids, the building blocks of proteins. Many universities, including MIT, have various equipment for the production of such peptides, but with the help of devices developed about 20 years ago, this process usually takes from two to six weeks. Such equipment takes about an hour to carry out the chemical reactions necessary to add one amino acid to the chain.
To speed up the process, MIT scientists adapted the synthesis reactions so that they could take place in a flow system. With this approach, the addition of a single amino acid takes only a few minutes, and the entire peptide can be assembled in just over an hour.
"In future versions, we think we'll be able to do each step in about 30 seconds," says Pentelut. "This means that we will really be able to do anything in a short period of time."
The new system has storage tanks for each of the 20 natural amino acids connected to pumps that allow you to supply the desired amino acid. Entering the chamber in which the reaction takes place, amino acids pass through the coil, where they are preheated to 60 degrees Celsius, which allows to accelerate the synthesis reaction.
The new system produces peptides of the same purity as the existing equipment. "We are on the same level with the most modern synthesis, but now we can do it much faster," continues Pentelut.
Chemists from MIT have developed a way to quickly assemble amino acids into protein fragments – peptides.
(Fig. Alexander Vinogradov)
According to Philip Dawson, an associate professor of chemistry at The Scripps Research Institute, who was not part of the research group, the system developed at MIT should facilitate the development and production of new peptides. "What I like about it is the simplicity of the device and the thoughtfulness with which everything is connected together," comments Professor Dawson. "I'm looking forward to testing it in my lab."
With this technology, scientists will be able to develop and quickly test new peptides for the treatment of cancer and other diseases, as well as create more effective versions of existing peptides, such as insulin, Pentelut continues. Another advantage of this high-speed approach is that any potential problems with the synthesis of a particular peptide can be detected much earlier, which will allow researchers to solve them immediately.
Another area that Pentelut plans to tackle is the creation of so–called "mirror" proteins. Almost all proteins existing in nature consist of L-amino acids and are right-rotating. The creation and study of peptides that mirror natural proteins can pave the way for the development of such peptides as new drugs with functions completely different from the properties of right-turning variants.
In a separate article published in the same issue of ChemBioChem (Rapid Total Synthesis of DARPin pE59 and Barnase), the researchers demonstrated that their technology can be used not only to synthesize peptides, but also to combine them into large synthetic proteins. To demonstrate this possibility, they created an antibody analog of 130 amino acids, as well as a 113-amino acid enzyme produced by bacteria.
The researchers have patented their technology, and the Deshpande Center for Technological Innovation (Deshpande Center for Technological Innovation) The Massachusetts Institute of Technology provided them with a grant to help in its commercialization. According to Pentelut, about 10 devices powered by the new technology will be enough to meet the current demand of 100,000 to 500,000 original peptides per year.
Professor Pentelut suggests that this technology may have an impact on the development of synthetic biology. It can be compared to the rapid synthesis of short strands of DNA and RNA. These chains – oligonucleotides – which take only one or two days to produce, can be used to create genes that give cells new functions.
"This is our goal – to deliver such peptide units anywhere in the world within one or two days. It's just a dream," the scientist sums up.
Portal "Eternal youth" http://vechnayamolodost.ru21.03.2014