title: Efficient solid-phase synthesis of pppRNA by using product-specific labeling.
abstract: A novel solid-phase synthesis and purification strategy for 5'-triphosphate oligonucleotides by using lipophilic tagging of the triphosphate moiety is reported. This is based on triphosphate synthesis with 5'-O-cyclotriphosphate intermediates, whereby a lipophilic tag, such as decylamine, is introduced during the ring-opening reaction to give a linear gamma-phosphate-tagged species. This method enables the highly efficient synthesis of 5'-triphosphorylated RNA derivatives and their gamma-phosphate-substituted analogues and will especially facilitate the advancement of therapeutic approaches that make use of 5'-triphosphate oligonucleotides as potent activators of the cytosolic immune sensor RIG-I.
authors.affiliation: Institute for Clinical Chemistry & Clinical Pharmacology, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127 Bonn (Germany).
authors.forename: M
authors.initials: M
authors.lastname: Goldeck
authors.forename: T
authors.initials: T
authors.lastname: Tuschl
authors.forename: G
authors.initials: G
authors.lastname: Hartmann
authors.forename: J
authors.initials: J
authors.lastname: Ludwig
mesh_terms: D002851:Chromatography, High Pressure Liquid; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D009841:Oligonucleotides / Q000737:chemistry*; D010766:Phosphorylation; D011122:Polyphosphates / Q000737:chemistry*; D012313:RNA / Q000138:chemical synthesis*; D011971:Receptors, Immunologic; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D009841:Oligonucleotides; D011122:Polyphosphates; D011971:Receptors, Immunologic; D012313:RNA; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; C005692:triphosphoric acid
keywords: RNA; immunology; medicinal chemistry; oligonucleotides; phosphorylation