New light labile linker for solid phase synthesis of 2'-O-acetalester oligonucleotides and applications to siRNA
Richard Johnsson1, Jeremy G Lackey, Jovanka J Bogojeski
1Department of Chemistry, McGill University, Montréal, Québec, Canada.
Abstract:
We report on the synthesis and properties of oligonucleotides containing 2'-O-(levulinic acid) and 2'-O-(amino acid) acetalesters. Given that esters serve as promoieties in several therapeutic prodrugs, we believe that these derivatives will have potential use as nucleic acid prodrugs. In addition, we report on the synthesis of a novel solid support with a photolabile linker that not only allows for the synthesis of oligonucleotides containing various 2'-O-acetalesters, but can be generally adopted to the synthesis of base-sensitive oligoribonucleotides. The release of oligonucleotides from this support is faster than with conventional linkers.
