title: Photouncaged Sequence-specific Interstrand DNA Cross-Linking with Photolabile 4-oxo-enal-modified Oligonucleotides.
abstract: DNA cross-linking technology is an attractive tool for the detection, regulation, and manipulation of genes. In this study, a series of photolabile 4-oxo-enal-modified oligonucleotides functionalized with photosensitive ο-nitrobenzyl derivatives were rationally designed as a new kind of photocaged cross-linking agents. A comprehensive evaluation of cross-linking reactions for different nucleobases in complementary strands under different conditions suggested that the modified DNA oligonucleotides tended to form interstrand cross-linking to nucleobases with the potential of thymidine > guanosine » cytidine ~ adenosine. Different from previous literature reports that cytidine and adenosine were preferential cross-linked nucleobases with 4-oxo-enal moieties, our study represents the first example of DNA cross-linking for T and G selectivity using 4-oxo-enal moiety. The cross-linked adducts were identified and their cross-linking mechanism was also illustrated. This greatly expands the applications of 4-oxo-enal derivatives in the studies of DNA damage and RNA structure.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, the School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, the School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China.
authors.forename: Xinjing
authors.initials: X
authors.lastname: Tang
mesh_terms: D001483:Base Sequence / Q000235:genetics; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003562:Cytidine / Q000737:chemistry / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics*; D004249:DNA Damage / Q000528:radiation effects; D009690:Nucleic Acid Conformation / Q000187:drug effects / Q000528:radiation effects; D009841:Oligonucleotides / Q000737:chemistry* / Q000235:genetics; D010095:Oxotremorine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D003432:Cross-Linking Reagents; D009841:Oligonucleotides; C042744:N-methylacetamide-oxotremorine M; D003562:Cytidine; D010095:Oxotremorine; D004247:DNA