Synthesis of proteins by automated flow chemistry
Author(s)
Hartrampf, Nina; Saebi, Azin; Poskus, M.; Gates, Zachary P; Callahan, A. J.; Cowfer, A. E.; Hanna, S.; Antilla, S.; Schissel, Carly K.; Quartararo, Anthony James; Ye, Xiyun; Mijalis, Alexander James; Simon, M. D.; Loas, Andrei Ioan; Liu, S.; Jessen, C.; Nielsen, T. E.; Pentelute, Bradley L.; ... Show more Show less
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Ribosomes can produce proteins in minutes and are largely constrained to proteinogenic amino acids. Here, we report highly efficient chemistry matched with an automated fast-flow instrument for the direct manufacturing of peptide chains up to 164 amino acids long over 327 consecutive reactions. The machine is rapid: Peptide chain elongation is complete in hours. We demonstrate the utility of this approach by the chemical synthesis of nine different protein chains that represent enzymes, structural units, and regulatory factors. After purification and folding, the synthetic materials display biophysical and enzymatic properties comparable to the biologically expressed proteins. High-fidelity automated flow chemistry is an alternative for producing single-domain proteins without the ribosome.
Date issued
2020-05Department
Massachusetts Institute of Technology. Department of ChemistryJournal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Hartrampf, N. et al. "Synthesis of proteins by automated flow chemistry." Science 368, 6494 (February 2020): 980-987 © 2020 American Association for the Advancement of Science
Version: Original manuscript
ISSN
0036-8075
1095-9203