Development of siRNA for therapeutics: efficient synthesis of phosphorothioate RNA utilizing phenylacetyl disulfide (PADS).
Efficient synthesis of phosphorothioate RNA (PS-RNA) is demonstrated by using phenylacetyl disulfide (PADS) in a mixture of pyridine and acetonitrile (1:1, v/v) for 3 min. Sulfurization is achieved with >99.8% stepwise efficiency. This reagent also performs efficiently during synthesis of RNA containing PS:PO mixed backbone.
Isis Pharmaceuticals, Inc., 2282 Faraday Avenue, Carlsbad, CA 92008, USA. vravikumar@isisph.com
Vasulinga T
VT
Ravikumar
Mark
M
Andrade
Recaldo L
RL
Carty
Amy
A
Dan
Steve
S
Barone
D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D010648:Phenylacetates / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D013440:Sulfides / Q000737:chemistry*; D013873:Thionucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*
D016376:Oligonucleotides, Antisense; D010648:Phenylacetates; D034741:RNA, Small Interfering; D013440:Sulfides; D013873:Thionucleotides; C511141:phenylacetyl disulfide