Cross-Linking Antisense Oligodeoxyribonucleotides with a Photoresponsive α‑Chloroaldehyde Moiety for RNA Point Mutations

• Published in: Journal of organic chemistry 2016-02, Vol.81 (3), p.981-986
• Main Authors: Sugihara, Yuta, Nakata, Yuki, Yamayoshi, Asako, Murakami, Akira, Kobori, Akio
• Format: Article
• Language: English
• Subjects: Adenosine - chemistry; Aldehydes - chemistry; GTP Phosphohydrolases - chemistry; GTP Phosphohydrolases - genetics; Indicators and Reagents - chemistry; Kinetics; Oligodeoxyribonucleotides, Antisense - chemistry; Point Mutation - genetics; RNA - chemistry; RNA - genetics
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b02573

Because point mutations in GTPase-coding genes have been reported to be responsible for the transformation of cells, anticancer reagents that react effectively and sequence selectively with target RNAs having a point mutation are highly desired. In this study, we developed novel photo-cross-linking oligodeoxyribonucleotides (proPCA-ODNs) that had a caged α-chloroaldehyde group conjugated to a 2-methylpropanediyl backbone (proPCA) in the middle of the strand. A kinetic study of the deprotection reaction of proPCA-ODN revealed that the bis­(2-nitrobenzyl)­acetal group was completely deprotected within 1 min. Photo-cross-linking studies of proPCA-ODNs with complementary oligoribonucleotides (ORNs) revealed that proPCA-ODNs reacts efficiently and selectively with the target ORNs that have an adenosine or cytidine residue at a frontal position of the proPCA residue without adverse effects of bases adjacent to the mutation site.