Synthesis of Sequence-Specific DNA鈥揚rotein Conjugates via a Reductive Amination Strategy

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• 作者：Susith Wickramaratne ; Shivam Mukherjee ; Peter W. Villalta ; Orlando D. Sch盲rer ; Natalia Y. Tretyakova
• 刊名：Bioconjugate Chemistry
• 出版年：2013
• 出版时间：September 18, 2013
• 年：2013
• 卷：24
• 期：9
• 页码：1496-1506
• 全文大小：568K
• 年卷期：v.24,no.9(September 18, 2013)
• ISSN：1520-4812

文摘

DNA鈥損rotein 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.