Site-selective installation of an electrophilic handle on proteins for bioconjugation.
Bioorganic & medicinal chemistry
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Lee, B., Sun, S., Jiménez-Moreno, E., Neves, A., & Lopes Bernardes, G. (2018). Site-selective installation of an electrophilic handle on proteins for bioconjugation.. Bioorganic & medicinal chemistry, 26 (11), 3060-3064. https://doi.org/10.1016/j.bmc.2018.02.028
Site-selective protein modification strategies can be used to insert non-natural functional groups into protein structures. Herein, we report on the use of the bis-electrophile 3-bromo-2-bromomethyl-1-propene as a reagent to introduce an electrophilic handle at cysteine residues under mild conditions. This method is demonstrated on a variety of proteins containing a solvent-exposed cysteine residue, including an anti-HER2 nanobody. Chemically distinct protein conjugates are then efficiently formed through further reaction of the electrophilic site with various nucleophiles, including thiols and amines. The resulting chemically-defined conjugates are highly stable in the presence of glutathione or human plasma and retain both the structure and function of the native protein.
Humans, Cysteine, Glutathione, Proteins, Circular Dichroism, Surface Plasmon Resonance, Models, Molecular, Antioxidant Response Elements
Royal Society (uf110046)
European Commission Horizon 2020 (H2020) ERC (676832)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (701473)
External DOI: https://doi.org/10.1016/j.bmc.2018.02.028
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275564
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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