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

The Journal of Organic Chemistry
Yuta SugiharaAkio Kobori

Abstract

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 ((pro)PCA-ODNs) that had a caged α-chloroaldehyde group conjugated to a 2-methylpropanediyl backbone ((pro)PCA) in the middle of the strand. A kinetic study of the deprotection reaction of (pro)PCA-ODN revealed that the bis(2-nitrobenzyl)acetal group was completely deprotected within 1 min. Photo-cross-linking studies of (pro)PCA-ODNs with complementary oligoribonucleotides (ORNs) revealed that (pro)PCA-ODNs reacts efficiently and selectively with the target ORNs that have an adenosine or cytidine residue at a frontal position of the (pro)PCA residue without adverse effects of bases adjacent to the mutation site.

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Citations

Mar 8, 2017·Bioorganic & Medicinal Chemistry·Kazumitsu OnizukaFumi Nagatsugi
Jun 24, 2017·Chemical Communications : Chem Comm·Shigetaka NakamuraKenzo Fujimoto
Jul 1, 2016·Chembiochem : a European Journal of Chemical Biology·Shigetaka NakamuraKenzo Fujimoto
Jul 12, 2021·Bioorganic & Medicinal Chemistry Letters·Ahmed Mostafa AbdelhadyFumi Nagatsugi
Apr 6, 2019·Organic Letters·Kazumitsu OnizukaFumi Nagatsugi
Jan 4, 2022·The Journal of Organic Chemistry·Ahmed Mostafa AbdelhadyFumi Nagatsugi

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