Prevention of chain cleavage in the chemical synthesis of 2′-silylated oligoribonucleotides
- 1 January 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 17 (9) , 3501-3517
- https://doi.org/10.1093/nar/17.9.3501
Abstract
Strong aqueous ammonium hyroxide used to remove N-acyl protecting groups from synthetic oligoribonucleotides causes removal of some alkylsilyl protecting groups from 2''-hydroxyls and leads to chain cleavage. This problem is most severe when 30% ammonium hydroxide is used and substantially reduced but still detectable when 3:1 ammonium hydroxide-ethanol is used. We have virtually eliminated this unwanted cleavage by incorporating the labile phenoxyacetyl amino protecting group on adenosine and guanosine. The N-benzoyl protecting group remains adequate for cytidine nucleosides. Synthetic oligoribonucleotides containing these N-acylated nucleosides and 2''-t-butyldimethylsilyl or 2''-triisopropyl protecting groups can be deacylated by room temperature treatment in saturated anhydrous methanolic ammonia (8-12 h) without causing any detectable chain cleavage.Keywords
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