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Issue 49, 2018
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Site-specific cross-linking of proteins to DNA via a new bioorthogonal approach employing oxime ligation

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Abstract

DNA–protein cross-links (DPCs) are super-bulky DNA adducts induced by common chemotherapeutic agents, reactive oxygen species, and aldehydes, and also formed endogenously as part of epigenetic regulation. Despite their presence in most cells and tissues, the biological effects of DPCs are poorly understood due to the difficulty of constructing site-specific DNA–protein conjugates. In the present work, a new approach of conjugating proteins to DNA using oxime ligation was used to generate model DPCs structurally analogous to lesions formed in cells. In our approach, proteins and peptides containing an unnatural oxy-Lys amino acid were cross-linked to DNA strands functionalized with 5-formyl-dC or 7-(2-oxoethyl)-7-deaza-dG residues using oxime ligation. The conjugation reaction was site-specific with respect to both protein and DNA, provided excellent reaction yields, and formed stable DPCs amenable to biological evaluation.

Graphical abstract: Site-specific cross-linking of proteins to DNA via a new bioorthogonal approach employing oxime ligation

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Publication details

The article was received on 14 Feb 2018, accepted on 23 May 2018 and first published on 24 May 2018


Article type: Communication
DOI: 10.1039/C8CC01300D
Citation: Chem. Commun., 2018,54, 6296-6299
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    Site-specific cross-linking of proteins to DNA via a new bioorthogonal approach employing oxime ligation

    S. S. Pujari, Y. Zhang, S. Ji, M. D. Distefano and N. Y. Tretyakova, Chem. Commun., 2018, 54, 6296
    DOI: 10.1039/C8CC01300D

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