Generation of DNA interstrand cross-links by post-synthetic reductive amination.
DNA interstrand cross-links (ICLs) are the clinically most relevant adducts formed by many antitumor agents. To facilitate the study of biological responses triggered by ICLs, we developed a new approach toward the synthesis of mimics of nitrogen mustard ICLs. 7-Deazaguanine residues bearing acetaldehyde groups were incorporated into complementary strands of DNA and cross-link formation induced by double reductive amination. Our strategy enables the synthesis of major groove cross-links in high yields and purity.
Angelov
Todor
T
Institute of Molecular Cancer Research, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Guainazzi
Angelo
A
Schärer
Orlando D
OD
D000586:Amination; D000970:Antineoplastic Agents / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D008466:Mechlorethamine / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D009841:Oligonucleotides; D008466:Mechlorethamine; D004247:DNA