Issue 26, 2021

Rapid and robust cysteine bioconjugation with vinylheteroarenes

Abstract

Methods for residue-selective and stable modification of canonical amino acids enable the installation of distinct functionality which can aid in the interrogation of biological processes or the generation of new therapeutic modalities. Herein, we report an extensive investigation of reactivity and stability profiles for a series of vinylheteroarene motifs. Studies on small molecule and protein substrates identified an optimum vinylheteroarene scaffold for selective cysteine modification. Utilisation of this lead linker to modify a number of protein substrates with various functionalities, including the synthesis of a homogeneous, stable and biologically active antibody–drug conjugate (ADC) was then achieved. The reagent was also efficient in labelling proteome-wide cysteines in cell lysates. The efficiency and selectivity of these reagents as well as the stability of the products makes them suitable for the generation of biotherapeutics or studies in chemical biology.

Graphical abstract: Rapid and robust cysteine bioconjugation with vinylheteroarenes

Supplementary files

Article information

Article type
Edge Article
Submitted
18 mei 2021
Accepted
28 mei 2021
First published
07 jun 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 9060-9068

Rapid and robust cysteine bioconjugation with vinylheteroarenes

H. Seki, S. J. Walsh, J. D. Bargh, J. S. Parker, J. Carroll and D. R. Spring, Chem. Sci., 2021, 12, 9060 DOI: 10.1039/D1SC02722K

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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