RESEARCHERS at MIT, US, have developed a fully-automated machine that can manufacture custom peptides to exact specifications in a fraction of the time previously achieved.
Many peptides – small protein molecules made up of chains of up to 50 amino acids – show promise as medicines and vaccines for diseases such as cancer, diabetes and bacterial infections. However, creating the desired peptide is conventionally a time-consuming process, taking around an hour to bond each amino acid onto the peptide chain. Now MIT associate chemistry professor Bradley Pentelute and his team have developed a machine that takes just 37 seconds to attach each amino acid.
The new machine could rapidly generate peptides and proteins for tests as drugs or vaccines, whether novel or inspired by nature. The peptides can be joined together to form longer proteins. For example, the team has already made HIV proteins, a fragment of a naturally-occurring antifreeze protein, a toxin from a type of snail, and some antimicrobial peptides, which some researchers believe could be a new class of antibiotics. Pentelute says that researchers can input whatever amino acids they want and the machine will simply produce them, faster than any other machine in the world.
The machine is based on flow chemistry, which works on the principal of chemicals flowing through modules which each perform a single stage of the reaction. The user must first input the desired amino acid sequence, after which the computer-controlled machine pumps in the amino acids in the correct order. As it is pumped in, the first module heats the amino acid to 90?C to make it more reactive. It then flows into a chamber where it connects to the forming peptide. By analysing the waste products, the researchers can work out how much of each amino acid was correctly incorporated into the peptide chain. The machine is around 99% accurate.
A previous version of the device, developed in 2014, took three minutes to create each amino acid bond and the amino acid input was controlled by hand. Having the process controlled by computer eliminates human error.
The researchers are looking to expand the number of peptides they can produce and are currently trying to make toxins from various animals which show potential as painkillers, blood thinners and blood clotting agents. They believe that their machine could also make peptides for personalised cancer vaccines, based on proteins found in individual patients’ tumours, a promising branch of cancer treatment.
“We can start thinking about a personalised chemistry machine. It’s modular and it’s adaptable to all sorts of other chemistries,” said Pentelute.
The team are looking at the possibility of adapting the technology to other long-chain molecules, such as polymers, RNA and DNA.
Nature Chemical Biology doi.org/b2fz
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