D-Altritol nucleic acids (ANA): Hybridisation properties, stability, and initial structural analysis

Abstract

Oligonucleotides composed of a phosphorylated D-altritol backbone with nucleobases introduced in the 2'-position, hybridise strongly and sequence-selectively with RNA in an antiparallel way. The order of hybridisation strength is: dsANA > ANA:RNA > ANA:DNA. Complexes between ANA and RNA dr DNA are more stable than between HNA and natural oligonucleotides. The dsANA hybrid is extremely stable. When compared with an identical dsDNA sequence, the Delta T-m per modification is 10.2 degrees C for a hexamer. CD spectral analysis indicates that ANA complexes are very similar to the A-form dsRNA duplex. ANA are stable in alkaline medium up to pH 12 and, likewise, are not degraded in human serum.