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Glutathione Mediates Control of Dual Differential Bio-orthogonal Labelling of Biomolecules |
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| Authors: | Dr. Frederik Peschke Dr. Andrea Taladriz-Sender Dr. Matthew J. Andrews Prof. Allan J. B. Watson Prof. Glenn A. Burley |
| Affiliation: | 1. Department of Pure & Applied Chemistry & the Strathclyde Centre for Molecular Bioscience, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL UK;2. EaStCHEM, School of Chemistry, University of Saint Andrews, North Haugh, St Andrews, Fife, KY16 9ST UK |
| Abstract: | Traditional approaches to bio-orthogonal reaction discovery have focused on developing reagent pairs that react with each other faster than they are metabolically degraded. 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. |
| Keywords: | bio-orthogonal chemistry ligation CuAAC peptide oligonucleotide |