title: New light labile linker for solid phase synthesis of 2'-O-acetalester oligonucleotides and applications to siRNA prodrug development.
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.
authors.affiliation: Department of Chemistry, McGill University, Montréal, Québec, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Johnsson
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Lackey
authors.forename: Jovanka J
authors.initials: JJ
authors.lastname: Bogojeski
authors.forename: Masad J
authors.initials: MJ
authors.lastname: Damha
mesh_terms: D000080:Acetals / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D019281:Dimerization; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D008027:Light; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry* / Q000378:metabolism; D013696:Temperature
chemical_list: D000080:Acetals; D004952:Esters; D009841:Oligonucleotides; D011355:Prodrugs; D034741:RNA, Small Interfering