Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Fast synthesis could boost drug development


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 $25 billion market by 2018.

However, a major bottleneck has prevented peptide drugs from reaching their full potential: Manufacturing the peptides takes several weeks, making it difficult to obtain large quantities, and to rapidly test their effectiveness.

That bottleneck may soon disappear: A team of MIT chemists and chemical engineers has designed a way to manufacture peptides in mere hours. The new system, described in the March 21st issue of 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," Pentelute says. "Because you can get these really fast now, you can start to do things you couldn't do before."

The lead author of the paper is Mark Simon, a graduate student in Pentelute's lab. Other authors include Klavs Jensen, head of MIT's Department of Chemical Engineering, and Andrea Adamo, a research associate in chemical engineering.

Accelerated manufacturing

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 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 researchers demonstrated that they could use this technology not only to synthesize peptides, but also combine these 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. Chemistry graduate students Surin Mong and Alexander Vinogradov are lead authors of that paper, along with Simon.

The researchers have patented the technology, and MIT's Deshpande Center for Technological Innovation has given them a grant to help commercialize it. Pentelute says he believes that about 10 machines using the new technology would be enough to meet current demand, which is about 100,000 to 500,000 custom peptides per year.

Pentelute envisions that the technology could have an impact on synthetic biology comparable to rapid synthesis of short strands of DNA and RNA. These strands, known as oligonucleotides, take only a day or two to prepare and can be used to create custom genes to give cells new functions.

"That's what our aim is — to have next-day or two-day delivery of these peptide units, to anyone in the world. That's really the dream," he says.


The research was funded by the MIT Reed Fund, the Deshpande Center, a Damon-Runyon-Rachleff Innovation Award, a Sontag Foundation Distinguished Scientist Award, a C.P. Chu and Y. Lai Fellowship, an AstraZeneca Distinguished Graduate Student Fellowship, the National Institute of General Medical Sciences, and the National Institutes of Health.

Written by Anne Trafton, MIT News Office

Sarah McDonnell | EurekAlert!

Further reports about: ChemBioChem MIT acid acids drugs manufacture peptides proteins synthesis synthetic

More articles from Health and Medicine:

nachricht Penn study stops vision loss in late-stage canine X-linked retinitis pigmentosa
13.10.2015 | University of Pennsylvania

nachricht Breast cancer drug beats superbug
13.10.2015 | University of California - San Diego

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Secure data transfer thanks to a single photon

Physicists of TU Berlin and mathematicians of MATHEON are so successful that even the prestigious journal “Nature Communications” reported on their project.

Security in data transfer is an important issue, and not only since the NSA scandal. Sometimes, however, the need for speed conflicts to a certain degree with...

Im Focus: A Light Touch May Help Animals and Robots Move on Sand and Snow

Having a light touch can make a hefty difference in how well animals and robots move across challenging granular surfaces such as snow, sand and leaf litter. Research reported October 9 in the journal Bioinspiration & Biomimetics shows how the design of appendages – whether legs or wheels – affects the ability of both robots and animals to cross weak and flowing surfaces.

Using an air fluidized bed trackway filled with poppy seeds or glass spheres, researchers at the Georgia Institute of Technology systematically varied the...

Im Focus: Reliable in-line inspections of high-strength automotive body parts within seconds

Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.

To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...

Im Focus: Kick-off for a new era of precision astronomy

The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.

As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...

Im Focus: Locusts at the wheel: University of Graz investigates collision detector inspired by insect eyes

Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.

Inspired by insects

All Focus news of the innovation-report >>>



Event News

EHFG 2015: Securing healthcare and sustainably strengthening healthcare systems

01.10.2015 | Event News

Conference in Brussels: Tracking and Tracing the Smallest Marine Life Forms

30.09.2015 | Event News

World Alzheimer`s Day – Professor Willnow: Clearer Insights into the Development of the Disease

17.09.2015 | Event News

Latest News

Smart clothing, mini-eyes, and a virtual twin – Artificial Intelligence at ICT 2015

13.10.2015 | Trade Fair News

Listening to the Extragalactic Radio

13.10.2015 | Physics and Astronomy

Penn study stops vision loss in late-stage canine X-linked retinitis pigmentosa

13.10.2015 | Health and Medicine

More VideoLinks >>>