Manufacturing small proteins known as peptides is usually very time-consuming, which has slowed development of new peptide drugs for diseases such as cancer, diabetes, and bacterial infections.
To help speed up the manufacturing process, MIT researchers have designed a machine that can rapidly produce large quantities of customized peptides. Their new tabletop machine can form links between amino acids, the buildings blocks of proteins, in about 37 seconds, and it takes less than an hour to generate complete peptide molecules containing up to 60 amino acids.
The team’s first version of a flow-based peptide synthesis machine, reported in 2014, sped up the process to about three minutes per peptide bond. In their latest effort, the researchers hoped to make the synthesis even faster by automating more of the process.
Once a user enters the desired amino acid sequence, the amino acids are pumped, in the correct order, into a module where they are briefly heated to about 900 Celsius to make them more chemically reactive. After being activated, the amino acids flow into a chamber where they are added to the growing peptide chains.
As each amino acid is added to the chain, the researchers can measure how much was correctly incorporated by analyzing the waste products that flow into the final chamber of the device. The current machine attaches each amino acid to the chain with about 99 percent efficiency.
Once synthesized, small peptides can be joined together to form larger proteins. So far, the researchers have made proteins produced by HIV, a fragment of an antifreeze protein (which helps organisms survive extreme cold), and a toxin secreted by snails. They are also working on replicating toxins from other animals, which have potential uses as painkillers, blood thinners, or blood clotting agents. They have also made antimicrobial peptides, which scientists are exploring as a possible new class of antibiotic drugs. Another possible application for the new machine is generating peptides that could be used as personalized cancer vaccines targeting unique proteins found in individual patients’ tumors.The MIT team is also interested in adapting this technology to make other molecules in which building blocks are strung together in long chains, such as polymers and oligonucleotides (strands of RNA or DNA).