Critical Effect of Base Pairing of Target Pyrimidine on the Interstrand Photo-Cross-Linking of DNA via 3-Cyanovinylcarbazole Nucleoside

Abstract

To evaluate the effect of base pairing of the target pyrimidine on the interstrand photo-cross-linking reaction of DNA via 3-cyanovinylcarbazole nucleoside ((CNV)K), a complementary base of target pyrimidine was substituted with noncanonical purine bases or 1,3-propandiol (S). As the decrease of the hydrogen bonds in the base pairing of target C accelerated the photo-cross-linking reaction markedly (3.6- to 7.7-fold), it can be concluded that the number of hydrogen bonds in the base pairing, i.e., the stability of base pairing, of the target pyrimidine plays a critical role in the interstrand photo-cross-linking reaction. In the case of G to S substitution, the highest photoreactivity toward C was observed, whose photoreaction rate constant (k = 2.0 s(-1)) is comparable to that of (CNV)K toward T paired with A (k = 3.5 s(-1)). This is the most reactive photo-cross-linking reaction toward C in the sequence specific interstrand photo-cross-linking. This might facilitate the design of the photo-cross-linkable oligodeoxyribonucleotides for various target sequences.

Study of Photochemical Cytosine to Uracil Transition via Ultrafast Photo-Cross-Linking Using Vinylcarbazole Derivatives in Duplex DNA

“…10 μM photo-cross-linked dsDNA was analyzed with HPLC system; elution was with 0.05 M ammonium formate containing 98–50% CH 3 CN, linear gradient (60 min) at flow rate of 1 mL/min. 4-Acetylpyridine, Aniline, Acetanilide, Phenol, Benzonitrile and Acetophenone were used as control compound to create calibration curve [ 26 , 27 ].…”

“…In 2015, we showed the effect of hydrogen bonding on the rate of the photo-cross-linking reaction by changing the counter-base of cytosine [ 26 ], which led to the idea that hydrogen bonding could also play a role in the deamination reaction. In 2017, we further proved our hypothesis by showing that certain counter-bases, especially inosine, of cytosine are better for deamination than other bases due to a specific type of hydrogen bonding in the cross-linked cytosine [ 27 ].…”

Templated DNA Cross‐Linking: Towards a Non‐Invasive Singlet‐Oxygen‐Based Triggering Method

“…[3][4][5][6] Recently, Fujimoto et al have described a crosslinking-assisted SNP genotyping, showing the potential of photo-crosslinks for biological applications. [7] In a more therapeutic context, it was extensively reported that blocking single stranded mRNA sequences through hybridization with their antisense complement leads to inhibition of expression and thus inhibition of the synthesis of the corresponding proteins. [8] Recently, various research groups have demonstrated that by introducing an ICL between a mRNA sequence and its antisense complement, the inhibitory effect becomes even more distinct.…”