title: Cross-Linking Antisense Oligodeoxyribonucleotides with a Photoresponsive α-Chloroaldehyde Moiety for RNA Point Mutations.
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.
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology , Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sugihara
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology , Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakata
authors.affiliation: The Hakubi Center for Advanced Research, Kyoto University , Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501, Japan.|Department of Chemistry, Graduate School of Science, Kyoto University , Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Yamayoshi
authors.affiliation: Kyoto Pharmaceutical University , Misasagi-Shichonocho 1, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Science and Technology, Kyoto Institute of Technology , Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kobori
mesh_terms: D000241:Adenosine / Q000737:chemistry*; D000447:Aldehydes / Q000737:chemistry*; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000235:genetics; D007202:Indicators and Reagents / Q000737:chemistry*; D007700:Kinetics; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry*; D017354:Point Mutation / Q000235:genetics*; D012313:RNA / Q000737:chemistry* / Q000235:genetics
chemical_list: D000447:Aldehydes; D007202:Indicators and Reagents; D020319:Oligodeoxyribonucleotides, Antisense; D012313:RNA; D020558:GTP Phosphohydrolases; D000241:Adenosine