Protein modification via alkyne hydrosilylation using a substoichiometric amount of ruthenium(II) catalyst
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Authors
Kwan, TT-L
Boutureira, O
Frye, EC
Gupta, MK
Wallace, S
Wu, Y
Zhang, F
Galloway, Warren
Publication Date
2017-05-01Journal Title
Chemical Science
ISSN
2041-6520
Publisher
Royal Society of Chemistry
Volume
8
Issue
5
Pages
3871-3878
Language
English
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Kwan, T., Boutureira, O., Frye, E., Walsh, S., Gupta, M., Wallace, S., Wu, Y., et al. (2017). Protein modification via alkyne hydrosilylation using a substoichiometric amount of ruthenium(II) catalyst. Chemical Science, 8 (5), 3871-3878. https://doi.org/10.1039/c6sc05313k
Abstract
Transition metal catalysis has emerged as a powerful strategy to expand synthetic flexibility of protein modification. Herein, we report a cationic Ru(II) system that enables the first example of alkyne hydrosilylation between dimethylarylsilanes and $\textit{O}$-propargyl-functionalized proteins using a substoichiometric amount or low-loading of Ru(II) catalyst to achieve the first C–Si bond formation on full-length substrates. The reaction proceeds under physiological conditions at a rate comparable to other widely used bioorthogonal reactions. Moreover, the resultant $\textit{gem}$-disubstituted vinylsilane linkage can be further elaborated through thiol–ene coupling or fluoride-induced protodesilylation, demonstrating its utility in further rounds of targeted modifications.
Sponsorship
This work was supported by the EU, EPSRC, BBSRC, MRC, Wellcome Trust and ERC (FP7/2007-2013; 279337/DOS). We thank Dr André Neves and Prof. Kevin Brindle for providing the C2Am protein. T. T.-L. Kwan acknowledges a scholarship from the Cambridge Trusts and the Croucher Foundation of Hong Kong and O. B. thanks the European Commission (Marie Curie IEF) for financial support. S. J. W. acknowledges a scholarship from AstraZeneca and the Cambridge Trusts. S. W. is the recipient of a Career Development Fellowship from the Medical Research Council. G. J. L. B. is a Royal Society University Research Fellow and the recipient of an ERC Staring Grant (TagIt). Work in the Chin lab was supported by the Medical Research Council, UK (MC_U105181009 and MC_UP_A024_1008) to J. W. C.
Funder references
Engineering and Physical Sciences Research Council (EP/J016012/1)
European Research Council (279337)
Royal Society (WM150022)
The Royal Society (uf110046)
European Research Council (676832)
Engineering and Physical Sciences Research Council (EP/M003647/1)
Engineering and Physical Sciences Research Council (EP/P020291/1)
European Commission (EC) (852985)
Identifiers
External DOI: https://doi.org/10.1039/c6sc05313k
This record's URL: https://www.repository.cam.ac.uk/handle/1810/264391
Rights
Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International, Attribution 4.0 International
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