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Discovery of a Serine-Directed Chemical Reaction for Site-Specific Protein Modification via Phage Display Screening

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION. 2025-10; 
Yingjie Lei, Kai Zhao, Mengzhun Guo, Liang Guo, Jinfeng Chen, Mengjiao Li, Dandan Liu, Kai Chen, Jiahao Mei, Tian Li, Bing Yang, Jing Huang, Bobo Dang
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Proteins, Expression, Isolation and Analysis The supernatant was loaded onto 2 mL Ni-Charged Resin (Genscript, Cat. NO. L00666-100), first washed with 40 mL of 20 mM Tris with 150 mM NaCl (pH 7.5), and then washed with 40 mL of 20 mM imidazole in 20 mM Tris with 150 mM NaCl (pH 7.5). Get A Quote

摘要

Conventional biocompatible chemistry typically depends on unnatural functional groups, such as alkynes and azides. Here, we present a natural amino acid-based alternative by leveraging phage display to discover CuII-assisted serine arylation (CASA), a serine-selective strategy for chemical protein modification, achieved through a CuII-mediated hydroxyl-arylation reaction. CASA enables fast and precise modification of a single serine hydroxyl group within complex proteins while leaving the other amino acids, including serines at other sites, unmodified. CASA demonstrates robust performance in on-demand modification of diverse recombinant proteins, including therapeutic antibodies, with single-residue precision. ... More

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