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Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho ‐Dithiophenols
Author(s) -
Li Youshan,
Lou Zhenbang,
Li Hongyun,
Yang Haijun,
Zhao Yufen,
Fu Hua
Publication year - 2020
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.201913620
Subject(s) - bioorthogonal chemistry , chemistry , combinatorial chemistry , conjugate , cleavage (geology) , click chemistry , biotinylation , fluorescence , stereochemistry , biochemistry , biology , mathematical analysis , mathematics , fracture (geology) , paleontology , physics , quantum mechanics
Abstract A bioorthogonal ligation and cleavage method via reactions of chloroquinoxalines (CQ) and ortho‐dithiophenols (DT) is presented. Double nucleophilic substitutions of ortho‐dithiophenols to chloroquinoxalines provide conjugates containing tetracyclic benzo[5,6][1,4]dithiino[2,3‐b]quinoxaline with strong built‐in fluorescence together with release of the other functional molecules. Three cleavable linkers were designed and successfully used in release of the molecules containing biotin from the protein conjugates. The CQ‐DT bioorthogonal reactions can be applied for the bioorthogonal ligations, bioorthogonal cleavages, and trans‐tagging of proteins, and show advantages of readily accessible unnatural orthogonal groups, appealing reaction kinetics (k 2 ≈1.3 m −1 s −1 ), excellent biocompatibility of orthogonal groups, and high stability of conjugates. This complements previous bioorthogonal reactions and is a new route for protein‐fishing applications and in‐gel fluorescence analysis.