2′-O-Carbamate-containing oligonucleotides: synthesis and properties

In order to evaluate the effect of a new 2′-carbohydrate modification on the hybridization properties of oligonucleotides, uridine 2′-O-carbamates were synthesized and incorporated into DNA strands. The key intermediate in the synthesis, a mixed succinimide carbonate 2, was treated with various amines to give 2′-O-carbamates 3. Thermal melting studies of modified oligonucleotides revealed that the presence of the 2′-O-carbamate modification significantly destabilized DNA/RNA duplexes. A molecular-modeling study indicated that unfavorable steric interactions between the hydrogen of the NH group from the carbamate substituent and the anomeric hydrogen of the sugar residue on the same strand of the duplex may be the contributing factor causing destabilization.