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Issue 42, 2020
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One-pot thiol–amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation

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Abstract

Maleimide chemistry is widely used in the site-selective modification of proteins. However, hydrolysis of the resultant thiosuccinimides is required to provide robust stability to the bioconjugates. Herein, we present an alternative approach that affords simultaneous stabilisation and dual functionalisation in a one pot fashion. By consecutive conjugation of a thiol and an amine to dibromomaleimides, we show that aminothiomaleimides can be generated extremely efficiently. Furthermore, the amine serves to deactivate the electrophilicity of the maleimide, precluding further reactivity and hence generating stable conjugates. We have applied this conjugation strategy to peptides and proteins to generate stabilised trifunctional conjugates. We propose that this stabilisation-dual modification strategy could have widespread use in the generation of diverse conjugates.

Graphical abstract: One-pot thiol–amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation

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Supplementary files

Article information


Submitted
16 Sep 2020
Accepted
23 Sep 2020
First published
02 Oct 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 11455-11460
Article type
Edge Article

One-pot thiol–amine bioconjugation to maleimides: simultaneous stabilisation and dual functionalisation

A. Wall, A. G. Wills, N. Forte, C. Bahou, L. Bonin, K. Nicholls, M. T. Ma, V. Chudasama and J. R. Baker, Chem. Sci., 2020, 11, 11455
DOI: 10.1039/D0SC05128D

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