A new class of nuclease-resistant oligonucleotides, consisting exclusively of α-anomeric nucleotide units, has been developped. The so called α-oligodeoxyribonucleotides were shown to strongly hybridize with complementary natural β-strands (DNA or RNA). The two complementary strands of α,β-duplexes adopt a parallel orientation and the double helix exists in aqueous solution in a conformation that belongs to the B family and is 70% right-handed. α-Oligodeoxynucleotides are competitive inhibitors, in vitro of HIV and M-MLV reverse transcriptases and E. Coli RNase H.