Synthesis of (2'S)- and (2'R)-2'-deoxy-2'-[(2-methoxyethoxy)amino] pyrimidine nucleosides and oligonucleotides.
Syntheses of specified 2'-modified nucleosides were achieved: a) via oximation of the 5',3'-blocked 2'-oxocytidine, followed by reduction, or b) by intramolecular nucleophilic addition of 3'-(2-methoxyethoxy)carbamate to the 2'-position with opening of O(2),2'-anhydrouridine. For the first time, 3'-phosphoroamidites of these 2'-modified nucleosides were successfully incorporated into oligonucleotides by solid-phase synthesis. Incorporation of 2'-modified nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex T(m) values with the DNA or RNA complements. Nevertheless, modified nucleotides have shown good target recognition; the (S)-isomer binds preferably to RNA and the (R)-isomer to DNA. Both modified nucleosides significantly increased nuclease resistance of the oligodeoxyribonucleotides.
Zatsepin
Timofei S
TS
Department of Chemistry, M. V. Lomonosov Moscow State University, Leninskie Gory, Moscow, Russia, 119992.
Ivanova
Yulia M
YM
Oretskaya
Tatiana S
TS
D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000302:isolation & purification; D027421:Persea; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000302:isolation & purification; D012910:Snake Venoms / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism
D009841:Oligonucleotides; D010936:Plant Extracts; D011741:Pyrimidine Nucleosides; D012910:Snake Venoms