Replacement of the furanose moiety of DNA with a cyclopentane ring produces a modified sugar analogue: Carbocyclic nucleic acid (CarNA). UV melting-temperature experiments demonstrate that the incorporation of 2´-deoxycarbaguanosine (^cG) and 2´-deoxyaristeromycin (^cA) of carbocyclic nucleosides into a DNA strand increases the stability of the CarNA/RNA hybrid. Circular Dichroism (CD) study indicates that the CarNA/RNA hybrid adopts an A-like conformation. To elucidate the molecular basis of the increased stability of the CarNA/RNA, the conformation of ^cG and ^cA were examined by ¹H NMR conformational analysis of ³J_HH coupling constants and ab initio molecular orbital (MO) calculations. These results show that the populations of N-type of ^cG and ^cA are higher than those of dG and dA, respectively, at different temperatures [For example, 37% (N%) of ^cG vs. 28% of dG, 36% (N%) of ^cA vs. 25% of dA at 278 K], which suggest that the cyclopentane rings of ^cG and ^cA prefer the N-type conformation in two-state N?S pseudorotional equilibrium in comparison with the furanose rings of dG and dA. The ΔH° of ^cG (ΔH° = ? 0.43 kcal mol^-1) and ^cA (ΔH° = ? 0.41kcal mol^-1) are lower than that of dG (dG = ? 1.8 kcal mol^-1) and dA (dA = ? 1.0 kcal mol^-1), respectively, which suggest that the gauche effect in the ^cA and ^cG driving N?S pseudorotional equilibrium to S-type is reduced by replacement of the 4´-oxygen by a CH₂ group. These results suggest that the preferred N-type of the ^cG and ^cA leads to the A-like conformation, which contributes to the stability of CarNA/RNA hybrid.

Key words: Carbocyclic nucleic acid, ³J_HH coupling constants, PSEUROT program, DNA conformation, Stability of DNA.