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Total chemical synthesis of proteins
Abstract
This tutorial review outlines the modern ligation methods that enable the efficient total chemical synthesis of enzymes and other protein molecules. Key to this success is the chemoselective reaction of unprotected synthetic peptides ('chemical ligation'). Notably, native chemical ligation enables the reaction of two unprotected peptides in aqueous solution at neutral pH to form a single product in near quantitative yield. Full-length synthetic polypeptides are folded to form the defined tertiary structure of the target protein molecule, which is characterized by mass spectrometry, NMR, and X-ray crystallography, in addition to biochemical and/or biological activity.
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Cited by
Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations
Agouridas, V., El Mahdi, O., Diemer, V., Cargoët, M., Monbaliu, J.-C. M., & Melnyk, O. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00712 · Cited by 650
Targeting the N terminus for site-selective protein modification
Rosen, C. B., & Francis, M. B. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2416 · Cited by 389
Synthesis of proteins by automated flow chemistry
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., et al. (2020) · Science · doi:10.1126/science.abb2491 · Cited by 367
Discovery, Synthesis, and Structure–Activity Relationships of Conotoxins
Akondi, K. B., Muttenthaler, M., Dutertre, S., Kaas, Q., Craik, D. J., Lewis, R. J., & Alewood, P. F. (2014) · Chemical Reviews · doi:10.1021/cr400401e · Cited by 323
van Dijk, M., Rijkers, D. T. S., Liskamp, R. M. J., van Nostrum, C. F., & Hennink, W. E. (2009) · Bioconjugate Chemistry · doi:10.1021/bc900087a · Cited by 300
Metadata
- Authors
- Kent, S. B. H.
- Venue
- Chem. Soc. Rev.
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2009
- Volume
- 38
- Issue
- 2
- Pages
- 338-351
- ISSN
- 0306-0012 (ISSN-L)
- 1460-4744
- OpenAlex
- W2025686590
- Cited by
- 922
- References
- 0
- FWCI
- 2.61
- Type
- journal article
- Language
- en
- Open access
- closed
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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