Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules

Frederik Peschke; Andrea Taladriz-Sender; Matthew J. Andrews; Allan J. B. Watson; Glenn Burley

doi:10.1002/anie.202313063

Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules

Frederik Peschke, Andrea Taladriz-Sender, Matthew J. Andrews, Allan J. B. Watson^*, Glenn Burley^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	e202313063
Number of pages	11
Journal	Angewandte Chemie International Edition
Volume	Early View
Early online date	31 Oct 2023
DOIs	https://doi.org/10.1002/anie.202313063
Publication status	E-pub ahead of print - 31 Oct 2023

Keywords

Bio-orthogonal chemistry
Ligation
CuAAC
Peptide
Oligonucleotide

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10.1002/anie.202313063Licence: CC BY

Peschke_2023_ACIE_Glutathione_CCBY
Copyright © 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 9.32 MBLicence: CC BY

A biochemical boron tagging stategy: A biochemical boron tagging strategy for biomolecule visualisation and profiling
Watson, A. J. B. (PI)
The Leverhulme Trust
1/09/22 → 31/08/24
Project: Fellowship
A Unified Approach to Bio-orthogonal: A Unified Approach to Bio-orthogonal Reaction Discovery in Living systems
Watson, A. J. B. (PI)
The Leverhulme Trust
1/06/21 → 30/11/23
Project: Standard
Chemoselective cross-coupling: Chemoselective cross-coupling via control of anion metathesis at Pd(II)
Watson, A. J. B. (PI)
EPSRC
1/07/18 → 31/08/22
Project: Standard

Cite this

@article{e9857bebb4a74f0fa08d2e9ad685a67a,

title = "Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules",

abstract = "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.",

keywords = "Bio-orthogonal chemistry, Ligation, CuAAC, Peptide, Oligonucleotide",

author = "Frederik Peschke and Andrea Taladriz-Sender and Andrews, {Matthew J.} and Watson, {Allan J. B.} and Glenn Burley",

note = "F.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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month = oct,

day = "31",

doi = "10.1002/anie.202313063",

language = "English",

volume = "Early View",

journal = "Angewandte Chemie International Edition",

issn = "1433-7851",

publisher = "John Wiley & Sons, Ltd",

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T1 - Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules

AU - Peschke, Frederik

AU - Taladriz-Sender, Andrea

AU - Andrews, Matthew J.

AU - Watson, Allan J. B.

AU - Burley, Glenn

N1 - F.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).

PY - 2023/10/31

Y1 - 2023/10/31

N2 - 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.

AB - 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.

KW - Bio-orthogonal chemistry

KW - Ligation

KW - CuAAC

KW - Peptide

KW - Oligonucleotide

U2 - 10.1002/anie.202313063

DO - 10.1002/anie.202313063

M3 - Article

SN - 1433-7851

VL - Early View

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

M1 - e202313063

ER -

Glutathione mediates control of dual differential bio‐orthogonal labelling of biomolecules

Abstract

Keywords

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Projects

A biochemical boron tagging stategy: A biochemical boron tagging strategy for biomolecule visualisation and profiling

A Unified Approach to Bio-orthogonal: A Unified Approach to Bio-orthogonal Reaction Discovery in Living systems

Chemoselective cross-coupling: Chemoselective cross-coupling via control of anion metathesis at Pd(II)

Cite this