Cleavable and tunable cysteine-specific arylation modification with aryl thioethers

• Published in: Chemical science (Cambridge) Vol. 12; no. 14; pp. 529 - 5215
• Main Authors: Li, Jian, Deng, Jun-Jie, Yin, Zhibin, Hu, Qi-Long, Ge, Yang, Song, Zhendong, Zhang, Ying, Chan, Albert S. C, Li, Huilin, Xiong, Xiao-Feng
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 18.02.2021; Royal Society of Chemistry; The Royal Society of Chemistry
• Subjects: Aromatic compounds; Biocompatibility; Chemistry; Chemistry, Multidisciplinary; Cysteine; Fluorescence; Peptides; Physical Sciences; Proteins; Regeneration; Science & Technology; Steric hindrance; FUNCTIONALIZATION; REACTIVITY; PEPTIDES; REAGENTS; BIOCONJUGATION; PROTEOME
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d0sc06576e

Cysteine represents an attractive target for peptide/protein modification due to the intrinsic high nucleophilicity of the thiol group and low natural abundance. Herein, a cleavable and tunable covalent modification approach for cysteine containing peptides/proteins with our newly designed aryl thioethers via a S N Ar approach was developed. Highly efficient and selective bioconjugation reactions can be carried out under mild and biocompatible conditions. A series of aryl groups bearing different bioconjugation handles, affinity or fluorescent tags are well tolerated. By adjusting the skeleton and steric hindrance of aryl thioethers slightly, the modified products showed a tunable profile for the regeneration of the native peptides. A cleavable and tunable covalent modification approach for cysteine by aryl thioethers via a S N Ar approach was developed. The highly efficient and selective bioconjugation reactions can proceed under the mild and biocompatible conditions.