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Exploration of the Reactivity of Multivalent Electrophiles for Affinity Labeling: Sulfonyl Fluoride as a Highly Efficient and Selective Label
Author(s) -
Suto Nanako,
Kamoshita Shione,
Hosoya Shoichi,
Sakurai Kaori
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202104347
Subject(s) - electrophile , chemistry , fluoride , reactivity (psychology) , photoaffinity labeling , ligand (biochemistry) , covalent bond , combinatorial chemistry , target protein , lysis , affinity labeling , affinity label , selectivity , binding site , biochemistry , organic chemistry , receptor , gene , inorganic chemistry , catalysis , medicine , alternative medicine , pathology
Here we explored the reactivity of a set of multivalent electrophiles cofunctionalized with a carbohydrate ligand on gold nanoparticles to achieve efficient affinity labeling for target protein analysis. Evaluation of the reactivity and selectivity of the electrophiles against three different cognate binding proteins identified arylsulfonyl fluoride as the most efficient protein‐reactive group in this study. We demonstrated that multivalent arylsulfonyl fluoride probe 4 at 50 n m concentration achieved selective affinity labeling and enrichment of a model protein PNA in cell lysate, which was more effective than photoaffinity probe 1 with arylazide group. Labeling site analysis by LC–MS/MS revealed that the nanoparticle‐immobilized arylsulfonyl fluoride group can target multiple amino acid residues around the ligand binding site of the target proteins. Our study highlights the utility of arylsulfonyl fluoride as a highly effective multivalent affinity label suitable for covalently capturing unknown target proteins.