MOLECULAR-DYNAMICS SIMULATION TO INVESTIGATE DIFFERENCES IN MINOR-GROOVE HYDRATION OF HNA RNA HYBRIDS AS COMPARED TO HNA/DNA COMPLEXES/

Hexitol nucleic acids (HNA) are oligonucleotides built up from natural nucleobases and a phosphorylated 1,5-anhydrohexitol backbone. Molecul ar associations between HNA and RNA are more stable than between HNA a nd DNA and between natural nucleic acids (dsDNA, dsRNA, DNA/RNA). H-1 NMR analysis of a HNA dimer confirms the axial orientation of the base moiety with respect to the hexitol ring, and this was used as startin g conformation for a molecular dynamics study of HNA/RNA and HNA/DNA d uplexes. Both complexes show an A-type geometry and very similar hydro gen bonding patterns between base pairs. The relative stability of HNA /RNA versus HNA/DNA might be explained by a difference in minor groove solvatation.