Synthesis of proteins by automated flow chemistry
The Pentelute Lab aims to invent new chemistry for the efficient and selective modification of proteins, to ‘hijack’ these biological machines for efficient drug delivery into cells and to create new machines to rapidly and efficiently manufacture peptides and proteins.
Pentelute Lab, Chemistry, MIT, Chemistry Department, Boston, Cambridge, Biology, Peptides, Peptide, Proteins, Science, Rapid, Brad Pentelute, Brad,
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Synthesis of proteins by automated flow chemistry

Synthesis of proteins by automated flow chemistry

Science 29 May 2020:
Vol. 368, Issue 6494, pp. 980-987
DOI: 10.1126/science.abb2491


N. Hartrampf, A. Saebi1, ProfileM. Poskus1, Z. P. Gates1, A. J. Callahan, A. E. Cowfer, S. Hanna, S. Antilla, ProfileC. K. Schissel, ProfileA. J. Quartararo1, X. Ye, A. J. Mijalis, M. D. Simon1, A. Loas, S. Liu, ProfileC. Jessen, T. E. Nielsen, B. L. Pentelute

Abstract

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.

Category
2020, Publications