Late-stage modification of peptides and proteins at cysteine with diaryliodonium salts

Stephen A Byrne; Max J Bedding; Leo Corcilius; Daniel J Ford; Yichen Zhong; Charlotte Franck; Mark Larance; Joel P Mackay; Richard J Payne

doi:10.1039/d1sc03127a

Late-stage modification of peptides and proteins at cysteine with diaryliodonium salts

Chem Sci. 2021 Sep 30;12(42):14159-14166. doi: 10.1039/d1sc03127a. eCollection 2021 Nov 3.

Authors

Stephen A Byrne^{1

2}, Max J Bedding^{1

2}, Leo Corcilius^{1

2}, Daniel J Ford^{1

2}, Yichen Zhong³, Charlotte Franck^{1

2

3}, Mark Larance^{3

4}, Joel P Mackay^{2

3}, Richard J Payne^{1

2}

Affiliations

¹ School of Chemistry, The University of Sydney Sydney NSW 2006 Australia [email protected].
² Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, The University of Sydney Sydney NSW 2006 Australia.
³ School of Life and Environmental Sciences, The University of Sydney Sydney NSW 2006 Australia.
⁴ Charles Perkins Centre, The University of Sydney NSW 2006 Australia.

Abstract

The modification of peptides and proteins has emerged as a powerful means to efficiently prepare high value bioconjugates for a range of applications in chemical biology and for the development of next-generation therapeutics. Herein, we report a novel method for the chemoselective late-stage modification of peptides and proteins at cysteine in aqueous buffer with suitably functionalised diaryliodonium salts, furnishing stable thioether-linked synthetic conjugates. The power of this new platform is showcased through the late-stage modification of the affibody zEGFR and the histone protein H2A.