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.
Krider
Elizabeth S
ES
Division of Biology and the Beckman Institute, California Institute of Technology, Pasadena, California 91125, USA.
Miller
Jeremiah E
JE
Meade
Thomas J
TJ
D000345:Affinity Labels; D002851:Chromatography, High Pressure Liquid; D006358:Hot Temperature; D006868:Hydrolysis; D009691:Nucleic Acid Denaturation; D009705:Nucleosides / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
D000345:Affinity Labels; D009705:Nucleosides; D009841:Oligonucleotides