The DOI matches its Crossref record; 71 of the 72 references it cites were found in a registry or an index.
Synthesis of proteins by automated flow chemistry
Open accessPublished version of a preprint
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.
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“However, notorious challenges, including base-induced racemization of seco-acids containing an α-chirality center,47Z/E isomerization of α, β-unsaturated seco-acids,48 and a competitive reaction involving intermolecular esterification leading to the formation of diolide side products have rendered it a formidable task.”
From Ynamide Coupling Reagents: Origin and Advances (2024) · cites this paper as [48]
Citations
Cites
Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide
Merrifield, R. B. (1963) · Journal of the American Chemical Society · doi:10.1021/ja00897a025 · Cited by 7,825
Principles that Govern the Folding of Protein Chains
Anfinsen, C. B. (1973) · Science · doi:10.1126/science.181.4096.223 · Cited by 7,096
Synthesis of Proteins by Native Chemical Ligation
Dawson, P. E., Muir, T. W., Clark‐Lewis, I., & Kent, S. B. H. (1994) · Science · doi:10.1126/science.7973629 · Cited by 4,190
Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53
Oliner, J. D., Pietenpol, J. A., Thiagalingam, S., Gyuris, J., Kinzler, K. W., & Vogelstein, B. (1993) · Nature · doi:10.1038/362857a0 · Cited by 1,474
Lutz, J., Ouchi, M., Liu, D. R., & Sawamoto, M. (2013) · Science · doi:10.1126/science.1238149 · Cited by 1,419
Peptide Coupling Reagents, More than a Letter Soup
El-Faham, A., & Albericio, F. (2011) · Chemical Reviews · doi:10.1021/cr100048w · Cited by 1,245
Synthesis of Native Proteins by Chemical Ligation
Dawson, P. E., & Kent, S. B. H. (2000) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.69.1.923 · Cited by 1,093
In situ neutralization in Boc‐chemistry solid phase peptide synthesis
Schnölzer, M., Alewood, P. F., Jones, A., Alewood, D., & Kent, S. B. H. (1992) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1992.tb00291.x · Cited by 1,055
Total chemical synthesis of proteins
Kent, S. B. H. (2008) · Chemical Society Reviews · doi:10.1039/b700141j · Cited by 927
Expanding and reprogramming the genetic code
Chin, J. W. (2017) · Nature · doi:10.1038/nature24031 · Cited by 740
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1 of the 72 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- M. D. Simon “Fast flow biopolymer synthesis ” thesis Massachusetts Institute of Technology Cambridge MA (2017).
- 10.1002/cbic.201300796 · DOI · Paper page
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Single-sequence protein structure prediction using a language model and deep learning
Chowdhury, R., Bouatta, N., Biswas, S., Floristean, C., Kharkar, A., Roy, K., Rochereau, C., Ahdritz, G., Zhang, J., Church, G. M., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01432-w · Cited by 455
Single-sequence protein structure prediction using language models from deep learning
Chowdhury, R., Bouatta, N., Biswas, S., Rochereau, C., Church, G. M., Sorger, P. K., & AlQuraishi, M. (2021) · doi:10.1101/2021.08.02.454840 · Cited by 455
Dissecting the role of protein phosphorylation: a chemical biology toolbox
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Conibear, A. C. (2020) · Nature Reviews Chemistry · doi:10.1038/s41570-020-00223-8 · Cited by 252
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Metadata
- Authors
- Hartrampf, N., Saebi, A., Poskus, M., Gates, Z. P., Callahan, A. J., Cowfer, A. E., Hanna, S., Antilla, S., Schissel, C. K., Quartararo, A. J., Ye, X., Mijalis, A. J., Simon, M. D., Loas, A., Liu, S., Jessen, C., Nielsen, T. E., & Pentelute, B. L.
- Affiliations
- Massachusetts Institute of Technology (US)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Saebi, A.
- Poskus, M.
- Pentelute, B. L.
- ORCID
- Venue
- Science
- Published
- 2020-05-29
- Volume
- 368
- Issue
- 6494
- Pages
- 980-987
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W3029756541
- Cited by
- 367
- References
- 72
- Citations by year
- 2026: 35 · 2025: 61 · 2024: 76 · 2023: 63 · 2022: 44 · 2021: 61 · 2020: 25
- FWCI
- 15.65
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-nd)
- Funders
- National Science Foundation (1122374)
- Novo Nordisk
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Physical Sciences › Chemical Engineering › Fluid Flow and Transfer Processes › Innovative Microfluidic and Catalytic Techniques Innovation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- protein synthesis, translation elongation, single-domain proteins, protein folding, enzyme activity, protein purification
- MeSH terms
- Protein Domains, Peptides, Proteins, Protein Folding, Solid-Phase Synthesis Techniques
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