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.

We developed a photoresponsive α-bromoaldehyde-conjugated oligonucleotide (PBA-ODN). The PBA-ODN selectively reacted and formed covalent bonds with target oligonucleotides having adenine or cytosine at the frontal position of the aldehyde derivative. Kinetic studies revealed that PBA-ODN has increased kinetic rates for the formation of cross-linked duplexes compared with the corresponding α-chloroaldehyde-conjugated oligonucleotide (PCA-ODN).

We have developed photoresponsive cross-linking oligodeoxyribonucleotides (ODNs) for sequence-selective interstrand covalent bond formation toward target nucleotides. A phosphoramidite derivative of α-chloroaldehyde whose carbonyl group was converted to a bis(2-nitrobenzyl)acetal group was prepared for the synthesis of photoresponsive α-chloroaldehyde (PCA)-conjugated ODN. The bis(2-nitrobenzyl)acetal group of a PCA–thymidine conjugate was completely removed by UV irradiation at 365 nm (400 mW/cm2) for 1 min. Photo-cross-linking studies revealed that PCA–ODN selectively reacted with the target nucleotides having an adenine or a cytosine moiety at the frontal position of the α-chloroaldehyde group.We have developed photoresponsive cross-linking oligodeoxyribonucleotides for sequence-selective interstrand covalent bond formation toward target nucleotides.

1,N6-Ethenoadenosine derivatives have been applied as fluorescence probes in various fields of biochemistry and molecular biology. We developed a 1,N6-ethenoadenosine-forming reaction at a target adenine in DNA duplex and applied it to a mutation diagnosis. Furan-derivatized oligodeoxyribonucleotides were synthesized and fluorescence properties were studied in the presence of complementary strand under oxidative conditions. Strong emissions at 430 nm were observed in the presence of the complementary strand with an adenine in front of furan moiety.We developed a 1,N6-ethenoadenosine-forming reaction at a target adenine in DNA duplex and applied it to a mutation diagnosis.