半胱氨酸
亲核细胞
试剂
化学
组合化学
噬菌体
氨基酸
硫醇
结合
肽
选择性
生物化学
有机化学
大肠杆菌
酶
催化作用
数学分析
基因
数学
作者
Fa-Jie Chen,Mengmeng Zheng,Vincent Nobile,Jianmin Gao
标识
DOI:10.1002/chem.202200058
摘要
This work reports a novel chlorooxime mediated modification of native peptides and proteins under physiologic conditions. This method features fast reaction kinetics (apparent k2 =306±4 M-1 s-1 for GSH) and exquisite selectivity for cysteine residues. This cysteine conjugation reaction can be carried out with just single-digit micromolar concentrations of the labeling reagent. The conjugates show high stability towards acid, base, and external thiol nucleophiles. A nitrile oxide species generated in situ is likely involved as the key intermediate. Furthermore, a bis-chlorooxime reagent is synthesized to enable facile Cys-Cys stapling in native peptides and proteins. This highly efficient cysteine conjugation and stapling was further implemented on bacteriophage to construct chemically modified phage libraries.
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