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 Jos�; Chan, Bun; Radom, Leo; Payne, Richard J.

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 ?-selenoaspartate and ?-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.

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

• Journal Article Type: Article
• Acceptance Date: Apr 11, 2017
• Online Publication Date: May 11, 2017
• Deposit Date: May 16, 2017
• Publicly Available Date: May 16, 2017
• Journal: Chem
• Electronic ISSN: 2451-9294
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 2
• Issue: 5
• DOI: https://doi.org/10.1016/j.chempr.2017.04.003
• Keywords: peptide synthesis; selenium; proteins; quantum chemistry calculations
• Public URL: https://nottingham-repository.worktribe.com/output/860280
• 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