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Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation.

ABSTRACT: Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via copper-assisted alkyne-azide cycloaddition (CuAAC) chemistry. We establish that these reagents are particularly effective at covalent modification of His-tags, which are common motifs to facilitate protein purification, as illustrated by selective attachment of polyarginine cargoes to enhance the uptake of proteins into living cells. This work provides a starting point for probing and enhancing protein function using histidine-directed chemistry.

SUBMITTER: Jia S

PROVIDER: S-EPMC6996876 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation.

Jia Shang S He Dan D Chang Christopher J CJ

Journal of the American Chemical Society 20190424 18

Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via ...[more]

PMID: 31017395

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