TY - JOUR
T1 - Synthesis of sequence-specific DNA-protein conjugates via a reductive amination strategy
AU - Wickramaratne, Susith
AU - Mukherjee, Shivam
AU - Villalta, Peter W.
AU - Schärer, Orlando D.
AU - Tretyakova, Natalia Y.
PY - 2013/9/18
Y1 - 2013/9/18
N2 - 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.
AB - 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.
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U2 - 10.1021/bc400018u
DO - 10.1021/bc400018u
M3 - Article
C2 - 23885807
AN - SCOPUS:84884398555
SN - 1043-1802
VL - 24
SP - 1496
EP - 1506
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 9
ER -