Title: Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation.
Authors: Jia, Shang; He, Dan; Chang, Christopher J
Published In J Am Chem Soc, (2019 05 08)
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.
PubMed ID: 31017395
MeSH Terms: Chlorides/chemistry; Chlorides/metabolism*; Histidine/chemistry; Histidine/metabolism*; Indicators and Reagents/chemistry; Indicators and Reagents/metabolism*; Molecular Structure; Phosphorus Compounds/chemistry; Phosphorus Compounds/metabolism*; Phosphorylation