Late-stage modification of peptides and proteins at cysteine with diaryliodonium salts
Stephen A. Byrne, Max J. Bedding, Leo Corcilius, Daniel Ford, Yichen Zhong, Charlotte Franck, Mark Larance, Joel P. Mackay, Richard J. Payne
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.
Topics & Concepts
CysteineChemistryCombinatorial chemistryBiochemistryPosttranslational modificationComputational biologyBiologyEnzymeChemical Synthesis and AnalysisClick Chemistry and ApplicationsPeptidase Inhibition and Analysis