Site-specific cross-linking of proteins to DNA

Via a new bioorthogonal approach employing oxime ligation

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)6296-6299
Number of pages4
JournalChemical Communications
Volume54
Issue number49
DOIs
StatePublished - Jan 1 2018

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Oximes
DNA
Proteins
DNA Adducts
Aldehydes
Peptides
Amino acids
Reactive Oxygen Species
Tissue
Amino Acids
Oxygen

PubMed: MeSH publication types

  • Journal Article

Cite this

Site-specific cross-linking of proteins to DNA : Via a new bioorthogonal approach employing oxime ligation. / Pujari, Suresh; Zhang, Yi; Ji, Shaofei; Distefano, Mark D; Tretyakova, Natalia Y.

In: Chemical Communications, Vol. 54, No. 49, 01.01.2018, p. 6296-6299.

Research output: Contribution to journalArticle

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