ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

Synthesis of Proteins by Automated Flow Chemistry

preprint
submitted on 11.02.2020, 01:46 and posted on 11.02.2020, 12:57 by Nina Hartrampf, Azin Saebi, Mackenzie Poskus, Zachary P. Gates, Alexander J. Callahan, Amanda E. Cowfer, Stephanie Hanna, Sarah Antilla, Carly K. Schissel, Anthony J. Quartararo, Xiyun Ye, Alexander J. Mijalis, Mark D. Simon, Andrei Loas, Shunying Liu, Carsten Jessen, Thomas E. Nielsen, Bradley L. Pentelute

Ribosomes produce most proteins of living cells in seconds. 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 over 328 consecutive reactions. The machine is rapid - the 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.

Funding

Novo Nordisk

History

Email Address of Submitting Author

nina.hartrampf@chem.uzh.ch

Institution

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Country

United States of America

ORCID For Submitting Author

0000-0003-0875-6390

Declaration of Conflict of Interest

Bradley L. Pentelute is a co-founder of Amide Technologies and Resolute Bio. Both companies focus on the development of protein and peptide therapeutics.

Exports