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We developed the base pair-mimic nucleosides tethering the phenyl group and the naphtyl group, synthesized from deoxyadenosine (Aphe and Anaph) and deoxycytidine (Cphe and Cnaph). Structure and the thermal stability of the DNA duplexes containing the deoxyadenosine derivatives or the deoxycytidine ones in the middle of a DNA strand were obtained by the CD spectra and the UV melting curves. The ΔGo37 values among DNA duplexes containing Aphe-A, Aphe-G, Aphe-C and Aphe-T pair differed only by 1.9 kcal mol−1. The DNA duplexes containing Cphe also showed the ΔGo37 values differed by 1.0 kcal mol-1 despite opposite base nucleotide, except the duplex containing the Cphe-G pair. Interestingly, the duplex consisting of the DNA containing the base pair-mimic nucleosides and the complementary RNA strand caused the site-selective RNA hydrolysis except the Cphe-G pair. This data suggests that the Cphe has an ability of forming the base pair with guanosine.

We previously reported that the deoxyadenosine derivative tethering the phenyl group at the N6 position of deoxyadenosine, Aphe stacked efficiently with the adjacent nucleotide bases at a DNA duplex terminus and in the middle of a DNA duplex. In contrast with the observations for Aphe, this study revealed that the phenyl group of the deoxycytidine derivative, Cphe located outside the helix and allowed the base pair formation with guanine in a DNA duplex, although its phenyl group could stack with the adjacent DNA bases as efficient as Aphe. Klenow fragment of DNA polymerase I and T7 DNA polymerase selectively incorporated dTTP and dGTP opposite Aphe and Cphe in the template DNA, respectively, implying that the conformation of Aphe differs between in the DNA polymerase and in solution.

On the basis of the non-covalent bond interactions in nucleic acids, we have synthesized a novel adenosine derivative tethering a phenyl group. Structure and thermal stability of the DNA duplexes bearing the adenosine derivative in the middle of a strand were investigated by CD spectra and the UV melting curves. We found that the conformation and the interactions of the duplexes were similar regardless of the nucleotide facing with the adenosine derivative in a duplex. This observation suggests the base pair-mimic geometry of the adenosine derivative accompanied with a conformational change of the nucleotide in the complementary strand.

We synthesized novel adenosine derivatives tethering an aromatic hydrocarbon group by an amido linker. The single adenosine derivatives at 5′ dangling end stabilized the DNA duplex of 5′-ATGCGCAT-3′ more or equally than Watson-Crick base pair. When the number of the dangling residues increased from one to three, the duplex stability became larger by 1.8∼3.6 kcal/mol. When the adenosine derivative was opposite to an abasic site in a DNA duplex, the destabilization by the abasic site was significantly reduced. These observations suggest that the adenosine derivatives developed in this study can stack with a DNA base pair by forming a base pair-mimic geometry.