Chemical Approach to Probing Different DNA Structures

DNA is polymorphic and exists in a variety of distinct conformations. Duplex DNA can adopt a variety of sequence-dependent secondary structures, which range from the canonical right-handed B form through to the left-handed Z form. Triplex and tetraplex structures also exist. All of these unique conformations are assumed to play important biological roles in processes such as DNA replication, and gene expression and regulation. However, the biological roles associated with the different structural conformations of DNA are not well understood because of the short lifetime of appearance of each structure and the difficulty in creating a system to demonstrate the DNA local structure. A stable Zform DNA under physiological salt conditions is needed to investigate the properties of Z-form DNA. To obtain stable Z-DNA, we synthesized various modified guanine derivatives and introduced these into oligonucleotides to evaluate their capacity to stabilize Z-form DNA. We found that incorporation of 8- methyl-2'-deoxyguanosine (m8G) and 8-methylguanosine (m8rG) into DNA dramatically stabilized the Z form, and facilitated the B-Z transition, even for ATcontaining sequences. Developing a Z-stabilizing monomeric unit, the Z stabilizer, allowed us to understand the solution structure of Z-DNA and to reveal the specific 2'β-hydrogen abstraction that gives rise to the Z-form-specific 2'a-hydroxylation of the IU-containing Z-form under UV irradiation. We also investigated the photoreaction of 5-halouracil in the A-form, B-form, G-quartet, and proteininduced DNA kinks. Hydrogen abstraction by 2'-deoxyuridin-5-yl generated from 5-halouracil under irradiation was atom specific and highly dependent on the DNA structure. In addition, DNA-mediated charge transport chemistry was sensitive to the DNA structure and base pair π-stacking. Ab initio molecular orbital calculation shows that the 5'-GG-3' sequence possessed the smallest vertical IP and that about 70% of the HOMO is localized on the 5'-G of 5'-GG-3' in B-form DNA. We propose that the electronic properties of DNA are highly dependent on the orientation of p-stacking (i.e., A-, B-, and Z-form DNA have different electronic properties). Furthermore, experimental studies show that bromouracil-containing Z-DNA has a unique electronic property, and that charge-transfer from G to BrU occurs efficiently within the four-base π-stacks in Z-DNA.