Synthesis and hybridization studies of alpha-configured arabino nucleic acids.

Synthesis of alpha-L-arabino- and alpha-D-arabino-configured pentofuranosyl nucleosides of four of the natural bases [thymine (ara-T), adenine (ara-A), cytosine (ara-C) and guanine (ara-G)] is reported together with hybridization properties of oligonucleotides containing alpha-L-ara-T and -A, alpha-D-ara-T and -A, and 2'-amino-alpha-L-ara-T monomers. 2'-O-Acetylated alpha-L-ara-T, -A, -C and -G, alpha-D-ara-T, -A, -C and -G, and N2'-acylated-alpha-L-ara-T phosphoramidite building blocks were synthesized and used together with standard DNA phosphoramidites for solid-phase synthesis of 18-mer oligonucleotides. Thermal denaturation experiments showed that incorporation of three or six of the arabino-configured monomers into DNA-oligonucleotides reduced the binding affinity towards antiparallel DNA/RNA complements. Fully modified alpha-L-ara-oligonucleotides did not hybridize with DNA/RNA complements, whereas hybridization of fully modified alpha-D-ara-oligonucleotides with complementary DNA/RNA in parallel strand orientation was confirmed.