2′-Modified nucleosides for site-specific labeling of oligonucleotides

We report the synthesis of 2′-modified nucleosides designed specifically for incorporating labels into oligonucleotides. Conversion of these nucleosides to phosphoramidite and solid support-bound derivatives proceeds in good yield. Large-scale synthesis of 11-mer oligonucleotides possessing the 2′-modified nucleosides is achieved using these derivatives. Thermal denaturation studies indicate that the presence of 2′-modified nucleosides in 11-mer duplexes has minimal destabilizing effects on the duplex structure when the nucleosides are placed at the duplex termini. The powerful combination of phosphoramidite and support-bound derivatives of 2′-modified nucleosides affords the large-scale preparation of an entirely new class of oligonucleotides. The ability to synthesize oligonucleotides containing label attachment sites at 3′, intervening, and 5′ locations of a duplex is a significant advance in the development of oligonucleotide conjugates.