Dinitroimidazoles as bifunctional bioconjugation reagents for protein functionalization and peptide macrocyclization
Qunfeng Luo,
Youqi Tao,
Wangjian Sheng,
Jingxia Lu and
Huan Wang ()
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Qunfeng Luo: Nanjing University
Youqi Tao: Nanjing University
Wangjian Sheng: Nanjing University
Jingxia Lu: Nanjing University
Huan Wang: Nanjing University
Nature Communications, 2019, vol. 10, issue 1, 1-9
Abstract:
Abstract Efficient and site-specific chemical modification of proteins under physiological conditions remains a challenge. Here we report that 1,4-dinitroimidazoles are highly efficient bifunctional bioconjugation reagents for protein functionalization and peptide macrocyclization. Under acidic to neutral aqueous conditions, 1,4-dinitroimidazoles react specifically with cysteines via a cine-substitution mechanism, providing rapid, stable and chemoselective protein bioconjugation. On the other hand, although unreactive towards amine groups under neutral aqueous conditions, 1,4-dinitroimidazoles react with lysines in organic solvents in the presence of base through a ring-opening & ring-close mechanism. The resulting cysteine- and lysine-(4-nitroimidazole) linkages exhibit stability superior to that of commonly employed maleimide-thiol conjugates. We demonstrate that 1,4-dinitroimidazoles can be applied in site-specific protein bioconjugation with functionalities such as fluorophores and bioactive peptides. Furthermore, a bisfunctional 1,4-dinitroimidazole derivative provides facile access to peptide macrocycles by crosslinking a pair of cysteine or lysine residues, including bicyclic peptides of complex architectures through highly controlled consecutive peptide macrocyclization.
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-018-08010-2
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DOI: 10.1038/s41467-018-08010-2
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