Synthesis of sequence-specific DNA-protein conjugates via a reductive amination strategy

Susith Wickramaratne, Shivam Mukherjee, Peter W. Villalta, Orlando D. Schärer, Natalia Y. Tretyakova

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


DNA-protein cross-links (DPCs) are ubiquitous, structurally diverse DNA lesions formed upon exposure to bis-electrophiles, transition metals, UV light, and reactive oxygen species. Because of their superbulky, helix distorting nature, DPCs interfere with DNA replication, transcription, and repair, potentially contributing to mutagenesis and carcinogenesis. However, the biological implications of DPC lesions have not been fully elucidated due to the difficulty in generating site-specific DNA substrates representative of DPC lesions formed in vivo. In the present study, a novel approach involving postsynthetic reductive amination has been developed to prepare a range of hydrolytically stable lesions structurally mimicking the DPCs produced between the N7 position of guanine in DNA and basic lysine or arginine side chains of proteins and peptides.

Original languageEnglish (US)
Pages (from-to)1496-1506
Number of pages11
JournalBioconjugate Chemistry
Issue number9
StatePublished - Sep 18 2013


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