Synthesis, duplex-forming properties, and enzymatic resistance of oligonucleotides containing N-acylsulfonamide linkages.

We report the synthesis of (2-(N-acetylsulfamoyl)ethyl)carbamate (NAC)-linked thymidine dinucleotide via the sulfo-click reaction and its incorporation into DNA oligonucleotides. Thermal denaturation studies indicate modest destabilization at duplex ends (∼1 °C) and stronger effects in the middle (∼7 °C), while the NAC linkage provides complete resistance to nucleases.