The acetal levulinyl ester (ALE) group for the 2'-hydroxyl protection of ribonucleosides and the synthesis of oligoribonucleotides.
A novel 2'-O-ALE (Acetal Levulinyl Ester) uridine phosphoramidite derivative has been efficiently prepared and used for the solid-phase synthesis of a chimeric oligonucleotide strand, 5'-rU11-dT-3'. The average coupling yield of the phosphoramidite was comparable to one obtained with a 2'-TBDMS rU phosphoramidite reagent. Upon completion of the RNA chain assembly, the cyanoethyl phosphate protecting groups were removed using a solution of triethylamine in acetonitrile (2:3 v/v). The 2'-O-ALE protecting groups were cleaved under hydrazinolysis conditions. Finally, the RNA oligonucleotide was released from the Q-CPG support when treated with 1 molar TBAF in THF. When the TBAF step was carried out prior to hydrazinolysis, an oligonucleotide with its intact 2'-O-ALE groups was obtained.
Lackey
Jeremy G
JG
Department of Chemistry, McGill University, Montreal, QC, Canada.
Damha
Masad J
MJ
D009843:Oligoribonucleotides / Q000138:chemical synthesis*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D034622:RNA Interference; D012263:Ribonucleosides / Q000737:chemistry*; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D009843:Oligoribonucleotides; D009943:Organophosphorus Compounds; D012263:Ribonucleosides; C434331:phosphoramidite; D014529:Uridine