Affiliation:
1. Graduate School of Biomedical Sciences Nagasaki University 1-14 Bunkyo-machi, Nagasaki Nagasaki 852-8521 Japan
2. SANKEN (The Institute of Scientific and Industrial Research) Osaka University 8-1 Mihogaoka Ibaraki Osaka 567-0047 Japan
3. IMRAM (Institute of Multidisciplinary Research for Advanced Materials) Tohoku University 2-1-1, Katahira, Aoba-ku Sendai 980-8577 Japan
Abstract
AbstractPsoralens and their derivatives, such as trioxsalen, have unique crosslinking features to DNA. However, psoralen monomers do not have sequence‐specific crosslinking ability with the target DNA. With the development of psoralen‐conjugated oligonucleotides (Ps‐Oligos), sequence‐specific crosslinking with target DNA has become achievable, thereby expanding the application of psoralen‐conjugated molecules in gene transcription inhibition, gene knockout, and targeted recombination by genome editing. In this study, we developed two novel psoralen N‐hydroxysuccinimide (NHS) esters that allow the introduction of psoralens into any amino‐modified oligonucleotides. Quantitative evaluation of the photo‐crosslinking efficiencies of the Ps‐Oligos to target single‐stranded DNAs revealed that the crosslinking selectivity to 5‐mC is the unique feature of trioxsalen. We found that the introduction of an oligonucleotide via a linker at the C‐5 position of psoralen can promote favorable crosslinking to target double‐stranded DNA. We believe our findings are essential information for the development of Ps‐Oligos as novel gene regulation tools.
Subject
Organic Chemistry,Molecular Biology,Molecular Medicine,Biochemistry
Cited by
2 articles.
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