Issue 23, 2018

Aryl transition metal chemical warheads for protein bioconjugation


The past seven years have witnessed the burgeoning of protein bioconjugation reactions highlighting aryl transition metal reagents as coupling partners. This new bioorthogonal organometallic chemistry, which sets the scene for stoichiometric processes in place of the catalytic procedures that developed in parallel, already enabled the forging of C–S and C–C bonds onto protein substrates, respectively in their native state or equipped with pre-installed non-natural terminal alkene or alkyne appendages. Although not yet applied to proteins, related transformations pointing to the creation of C–N bonds have, in addition, just been disclosed by targeting peptide lysine residues. Central to this research was the selection of ligands attached to the transition metal, in order to confer to metal complexes, not only their stability in aqueous medium, but also the desired chemoselectivity. We summarize here this body of work, which has already put in the limelight elaborated palladium and gold complexes equipped with biologically relevant appendages, such as fluorescent and affinity tags, as well as drug molecules. This research holds much promise, not only for the study of proteins themselves, but also for the design of new protein-based biotherapeutics, such as protein-drug conjugates or constrained analogs resulting from macrocyclisation reactions.

Graphical abstract: Aryl transition metal chemical warheads for protein bioconjugation

Article information

Article type
16 Feb 2018
22 May 2018
First published
23 May 2018
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., 2018,9, 5132-5144

Aryl transition metal chemical warheads for protein bioconjugation

P. Bisseret, H. Abdelkafi and N. Blanchard, Chem. Sci., 2018, 9, 5132 DOI: 10.1039/C8SC00780B

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.

Read more about how to correctly acknowledge RSC content.

Social activity