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Accelerated protein synthesis via one–pot ligation–deselenization chemistry

Mitchell, Nicholas J.; Sayers, Jessica; Kulkarni, Sameer S.; Clayton, Daniel; Goldys, Anna M.; Ripoll-Rozada, Jorge; Barbosa Pereira, Pedro José; Chan, Bun; Radom, Leo; Payne, Richard J.

Authors

Jessica Sayers

Sameer S. Kulkarni

Daniel Clayton

Anna M. Goldys

Jorge Ripoll-Rozada

Pedro José Barbosa Pereira

Bun Chan

Leo Radom

Richard J. Payne



Abstract

Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future.

Journal Article Type Article
Journal Chem
Electronic ISSN 2451-9294
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 2
Issue 5
APA6 Citation Mitchell, N. J., Sayers, J., Kulkarni, S. S., Clayton, D., Goldys, A. M., Ripoll-Rozada, J., …Payne, R. J. (in press). Accelerated protein synthesis via one–pot ligation–deselenization chemistry. Chem, 2(5), https://doi.org/10.1016/j.chempr.2017.04.003
DOI https://doi.org/10.1016/j.chempr.2017.04.003
Keywords peptide synthesis; selenium; proteins; quantum chemistry calculations
Publisher URL http://www.sciencedirect.com/science/article/pii/S2451929417301699
Related Public URLs http://www.cell.com/action/showAbstract?pii=S2451-9294%2817%2930169-9&doi=10.1016%2Fj.chempr.2017.04.003
Copyright Statement Copyright information regarding this work can be found at the following address: http://eprints.nottingh.../end_user_agreement.pdf

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://eprints.nottingham.ac.uk/end_user_agreement.pdf





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