Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules
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Traditional approaches to bio‐orthogonal reaction discovery have focused on developing reagent pairs that react faster with each other than their metabolic degradation. Glutathione (GSH) is typically responsible for the deactivation of most bio‐orthogonal reagents. Here we demonstrate that GSH promotes a Cu‐catalysed (3+2) cycloaddition reaction between an ynamine and an azide. We show that GSH acts as a redox modulator to control the Cu oxidation state in these cycloadditions. Rate enhancement of this reaction is specific for ynamine substrates and is tuneable by the Cu:GSH ratio. This unique GSH‐mediated reactivity gradient is then utilised in the dual sequential bio‐orthogonal labelling of peptides and oligonucleotides via two distinct chemoselective (3+2) cycloadditions.
Peschke , F , Taladriz-Sender , A , Andrews , M J , Watson , A J B & Burley , G 2023 , ' Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules ' , Angewandte Chemie International Edition , vol. Early View , e202313063 . https://doi.org/10.1002/anie.202313063
Angewandte Chemie International Edition
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DescriptionF.P., A.J.B.W. and G.A.B. thank the University of Strathclyde for a PhD studentship and the Leverhulme Trust for a research grant (RPG-2020-380). A.T.S. and G.A.B. thank the Biotechnology and Biological Research Council for their support (BB/R006857/1). A.J.B.W. and M.J.A. thank the Engineering and Physical Sciences Research Council for their support (EP/R025754/1). A.J.B.W. thanks the Leverhulme Trust for a research fellowship (RF-2022-014).
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