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

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.

SUBMITTER: Byrne SA

PROVIDER: S-EPMC8565360 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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

Byrne Stephen A SA Bedding Max J MJ Corcilius Leo L Ford Daniel J DJ Zhong Yichen Y Franck Charlotte C Larance Mark M Mackay Joel P JP Payne Richard J RJ

Chemical science 20210930 42

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 ...[more]

PMID: 34760200

Similar Datasets

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

Project description: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.

2022-02-16 | PXD028382 | Pride

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Fast and Cysteine-Specific Modification of Peptides, Proteins and Bacteriophage Using Chlorooximes.

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Project description:Phenols, anilines, and malonates have been arylated under metal-free conditions with twelve aryl(phenyl)iodonium salts in a systematic chemoselectivity study. A new "anti-ortho effect" has been identified in the arylation of malonates. Several "dummy groups" have been found that give complete chemoselectivity in the transfer of the phenyl moiety, irrespective of the nucleophile. An aryl exchange in the diaryliodonium salts has been observed under certain arylation conditions. DFT calculations have been performed to investigate the reaction mechanism and to elucidate the origins of the observed selectivities. These results are expected to facilitate the design of chiral diaryliodonium salts and the development of catalytic arylation reactions that are based on these sustainable and metal-free reagents.

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