Synthesis and properties of l-lyxo-thioBsNA-pyrimidine nucleoside: a sulfur-containing analogue of boat-shaped pyranosyl nucleic acid

Abstract

L-lyxo-thioBsNA, a boat-shaped nucleic acid (BsNA) analogue designed to enhance hydrophobicity – a property strongly influencing its physical characteristics – was synthesized. Oligonucleotides containing L-lyxo-thioBsNA were efficiently synthesized using the phosphoramidite method with levulinyl chemistry, and their hydrophobicity was higher than that achieved using PS-modification, as revealed by analysis using reverse-phase HPLC. The double helix with the complementary RNA strand is highly stable, and the introduction of sulfur atoms with large atomic radii did not adversely affect thermal stability. These characteristics demonstrate that L-lyxo-thioBsNA is an ideal nucleic acid modifier for RNA-targeting technologies such as antisense methods, offering a new option for use in situations requiring hydrophobic nucleic acids.