Homo-N-oligonucleotides (N1/N9−C1‘ Methylene Bridge Oligonucleotides): Nucleic Acids with Left-Handed Helicity

Abstract

Oligonucleotides containing a methylene bridge between N1 or N9 of the heterocyclic base and C1' of the pentofuranosyl ring (homo-N-oligonucleotides) were synthesized. Melting curves revealed that such homo-type oligomers could cross-pair with complementary homo-type or natural oligomers. Circular-dichroic studies provide evidence that the homo-type dimers have a left-handed stacked conformation and further suggest that single-stranded and double-stranded homo-type oligomers adopt a left-handed conformation, while duplexes with natural oligomers or nucleic acids form RNA-like right-handed helices. NMR spectroscopy (NOESY) provides supporting evidence for a left-handed stacked conformation of the homo-type dimer, while atomic force microscopy indicates a left-handed helical conformation of homo-type dsDNA. Homo-type dimers and oligomers showed high resistance to digestion by snake-venom and calf-spleen phosphodiesterases and nuclease S1.