Fast and Cysteine-Specific Modification of Peptides, Proteins and Bacteriophage Using Chlorooximes.

ABSTRACT: 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 bacteriop

SUBMITTER: Chen FJ 

PROVIDER: S-EPMC8986619 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature