Home Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports
Article
Licensed
Unlicensed Requires Authentication

Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports

  • Michael Gerster , Martin Maier , Nils Clausen , Jens Schewitz and Ernst Bayer
Published/Copyright: June 2, 2014
Become an author with De Gruyter Brill
Author Information Explore this Subject
Zeitschrift für Naturforschung B
From the journal Zeitschrift für Naturforschung B Volume 52 Issue 1

Sulphurization is a crucial step during synthesis of phosphorothioate oligonucleotides. Insufficient reaction leads to inhomogeneous products with phosphodiester defects and subsequently to destabilization of the oligomers in biological media. To achieve a maximum extent of sulphur incorporation, various sulphurizing agents have been investigated. Solely, the use of Beaucage reagent provided satisfactory results on PS-PEG supports. Based on our investigations in small scale synthesis (1 μmol) with continuous-flow technique, upscaling to the 0.1-0.25 mmolar range has been achieved using a peptide synthesizer. The syntheses were performed in batch mode with standard phosphoramidite chemistry. Additionally, large scale synthesis of a phosphodiester oligonucleotide has been carried out on PS-PEG with optimized protocols and compared to small scale synthesis on different supports. Products were analysed by 31P NMR, capillary gel electrophoresis and electrospray mass spectrometry. An extent of sulphurization of 99% and coupling effiencies of more than 99% were obtained and the products proved to have similar purity compared to small scale syntheses on CPG

: Large Scale Synthesis; Oligonucleotide Phosphorothioate; PS-PEG; Sulphurizing Reagent
Received: 1996-9-11
Published Online: 2014-6-2
Published in Print: 1997-1-1

© 1946 – 2014: Verlag der Zeitschrift für Naturforschung

Articles in the same Issue

  1. Contents
  2. Synthese und Untersuchung neuer 1λ5, 4λ5-Diphosphapentalen- und 1λ5,4λ5 - sowie 1λ5,5λ5-Diphosphaazulen-Systeme / Synthesis of New 1λ5,4λ5-Diphosphapentalene- and 1λ5,5λ5-Diphosphaazulene Systems
  3. Synthese und Reaktivität von γ-Triphenylstannyl-α-aminobuttersäure-derivaten / Synthesis and Reactivity of γ-Triphenylstannyl-α-aminobutyric Acid Derivatives
  4. Coordination Chemistry of Lipoic Acid and Related Compounds, Part 1 Syntheses and Crystal Structures of the UV- and Light-Sensitive Lipoato Complexes [M(lip)2(H2O)2] (M = Zn, Cd)
  5. Photochemische Synthese neuer zinnorganischer Verbindungen mit „aktiven“ Gruppen am Zinnatom (I) / Photochemical Synthesis of New Tinorganic Compounds with Active Substituents on Tin
  6. 1-Allylgermatrane. Synthesis, Structure and Reaction with Diazomethane
  7. Über die Kristallstrukturen der Tellurate Pb3Fe2Te2O12 und Pb2CoTeO6 / On the Crystal Structures of the Tellurates Pb3Fe2Te2O12 and Pb2CoTeO6
  8. Synthese von 1-Butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadien und seiner Natrium-, Thallium(I)-und Eisen(II)-Komplexe / Synthesis of 1-Butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadiene and its Sodium, Thallium (I) and Iron(II) Complexes
  9. 1,4-Bis(4-acylphen-1 -yl) 1,3-cy clopentadiene und 1,2,3,4-Tetra(4-alkylphen-1-yl)-1,3-cyclopentadiene und deren Natrium-, Thallium(I)- und Eisen(II)-Komplexe / 1,4-Bis(4-acylphen-1-yl)-1,3-cyclopentadienes and 1,2,3,4-Tetra(4-alkylphen-1-yl)- 1,3-cyclopentadienes and their Sodium, Thallium (I) and Iron(II) Complexes
  10. Structural Investigation of Bis(isonitrile)gold(I) Complexes
  11. Darstellung und spektroskopische Charakterisierung von (η3-Hexahydro-closo-hexaborato)phenylquecksilber(1-) [Hg(η3-B6H6)Ph] sowie Kristallstruktur von [PPh4][Hg(η3-B6H6)Ph] / Preparation and Spectroscopic Characterization of (η3-Hexahydro-closo-hexaborato)phenylmercury(1 -) [Hg(η3-B6H6)Ph]- and Crystal Structure of [PPh4][Hg(η3-B6H6)Ph]
  12. Ligandenaustauschreaktionen von ReCl4(PPh3)2 mit Salicylaldehyd-2-hydroxy(mercapto)anil. Struktur von Bis[salicylaldehyd-2-hydroxyanilato(2-)]rhenium(IV) / Ligand Exchange Reactions of ReCl4 (PPh3)2 with Salicylaldehyde-2-hydroxy(mercapto)anil. Molecular Structure of Bis[salicylaldehyde-2-hydroxyanilato(2-)]rhenium(IV)
  13. Charge - Transfer Complexes of Metal Dithiolenes XXIV: Ion Pairs of the Tetrakis(dimethylamino)ethene Dication with Dithiolene Metalate Dianions
  14. Bis(trifluormethyl)disulfan und -trisulfan: Molekülgeometrie im festen Zustand [1] / Bis(trifluoromethyl)disulfane and Trisulfane: Molecular Geometry in the Solid State [1]
  15. 1,3-Dioxolane von N-substituierten 4-Piperidonen als Dehydrierungssubstrat / 1,3-Dioxolanes of N-Substituted 4-Piperidones as Substrates for Dehydrogenations
  16. Synthesis and Structure of Bis[di(methylcyclopentadienyl)chloro-titanium]trisulfide [(Cp′2ClTi)2S3] - a Reagent for Trisulfide Ligand Transfer Reactions [1]
  17. Ba(VO)4(AsO4)2(As2O7): Ein neues Divanadyl(IV)-Arsenat mit flächenverknüpften V2O8+1-Oktaederdoppeln / Ba(VO)4 (AsO4)2 (As2O7): A New Divanadyl(IV)-Arsenate Containing Face Shared V2O8+, Double Octahedra
  18. Über die Darstellung von CH3C6H4S(O)2NCl2H+SbF-6 und die Kristallstruktur von CH3C6H4S(O)2NCl2 / On the Synthesis of CH3C6H4S(O)2NCl2,H+SbF-6 and the Crystal Structure of CH3C6H4S(O)2NCl2
  19. Bis-und Tris[μ-nitrido-bis(diorganylphoshinato-O,O′)]- element( 1+)-Kationen / Bis- and Tris[μ-nitrido-bis(diorganylphosphinato-O,O′)]-element(1+) Cations
  20. Die Synthese und Kristallstruktur des Borat-Phosphats: α -Zn3(BO3)(PO4) / Synthesis and Crystal Structure of the Borate-Phosphate: α-Zn3(BO3)( PO4)
  21. Occurrence of Toxin Producing Cyanobacteria in Hungary. Isolation, Separation and Identification of Microcystins
  22. Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports
  23. Synthesis of Cationic Ruthenium Thioketene Complexes through Intramolecular 1,2-Elimination [1]
  24. Eindimensionale Kupfer(II)-Koordinationspolymere: Kristall-Engineering durch variable Verknüpfungsmuster [1] / One Dimensional Copper(II) Coordination Polymers: Crystal Engineering through Variable Types of Linkage [1]
  25. Darstellung und spektroskopische Charakterisierung von Trifluormethylazosulfonylmethan CH3S(O) 2NNCF3 / Preparation and Spectroscopic Characterization of Trifluoromethylazosulfonylmethan CH3S(O)2NNCF3
  26. Kristallstruktur von 1,1,1-Trichloro-cyclo-1λ6-wolframa-3,5-dithia-2,4,6- triazin, [WCl3(N3S2 )]2 / Crystal Structure of 1,1,1-Trichloro-cyclo- 1λ6-tungsta-3,5-dithia-2,4,6-triazine, [WCl3(N3S2)]2
  27. The Stannide Zr5CuSn3
  28. Die Kristallstruktur von Tris(trimethylstannyl) acetonitril / Crystal Structure of Tris(trimethylstannyl)- acetonitrile
  29. Die Kristallstrukturen von Trimethylbleiiodid und Diphenylbismutchlorid / Crystal Structures of Trimethyllead Iodide and Diphenylbismuth Chloride
https://doi.org/10.1515/znb-1997-0122

Articles in the same Issue

  1. Contents
  2. Synthese und Untersuchung neuer 1λ5, 4λ5-Diphosphapentalen- und 1λ5,4λ5 - sowie 1λ5,5λ5-Diphosphaazulen-Systeme / Synthesis of New 1λ5,4λ5-Diphosphapentalene- and 1λ5,5λ5-Diphosphaazulene Systems
  3. Synthese und Reaktivität von γ-Triphenylstannyl-α-aminobuttersäure-derivaten / Synthesis and Reactivity of γ-Triphenylstannyl-α-aminobutyric Acid Derivatives
  4. Coordination Chemistry of Lipoic Acid and Related Compounds, Part 1 Syntheses and Crystal Structures of the UV- and Light-Sensitive Lipoato Complexes [M(lip)2(H2O)2] (M = Zn, Cd)
  5. Photochemische Synthese neuer zinnorganischer Verbindungen mit „aktiven“ Gruppen am Zinnatom (I) / Photochemical Synthesis of New Tinorganic Compounds with Active Substituents on Tin
  6. 1-Allylgermatrane. Synthesis, Structure and Reaction with Diazomethane
  7. Über die Kristallstrukturen der Tellurate Pb3Fe2Te2O12 und Pb2CoTeO6 / On the Crystal Structures of the Tellurates Pb3Fe2Te2O12 and Pb2CoTeO6
  8. Synthese von 1-Butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadien und seiner Natrium-, Thallium(I)-und Eisen(II)-Komplexe / Synthesis of 1-Butyl-2,3,4,5-tetraphenyl-2,4-cyclopentadiene and its Sodium, Thallium (I) and Iron(II) Complexes
  9. 1,4-Bis(4-acylphen-1 -yl) 1,3-cy clopentadiene und 1,2,3,4-Tetra(4-alkylphen-1-yl)-1,3-cyclopentadiene und deren Natrium-, Thallium(I)- und Eisen(II)-Komplexe / 1,4-Bis(4-acylphen-1-yl)-1,3-cyclopentadienes and 1,2,3,4-Tetra(4-alkylphen-1-yl)- 1,3-cyclopentadienes and their Sodium, Thallium (I) and Iron(II) Complexes
  10. Structural Investigation of Bis(isonitrile)gold(I) Complexes
  11. Darstellung und spektroskopische Charakterisierung von (η3-Hexahydro-closo-hexaborato)phenylquecksilber(1-) [Hg(η3-B6H6)Ph] sowie Kristallstruktur von [PPh4][Hg(η3-B6H6)Ph] / Preparation and Spectroscopic Characterization of (η3-Hexahydro-closo-hexaborato)phenylmercury(1 -) [Hg(η3-B6H6)Ph]- and Crystal Structure of [PPh4][Hg(η3-B6H6)Ph]
  12. Ligandenaustauschreaktionen von ReCl4(PPh3)2 mit Salicylaldehyd-2-hydroxy(mercapto)anil. Struktur von Bis[salicylaldehyd-2-hydroxyanilato(2-)]rhenium(IV) / Ligand Exchange Reactions of ReCl4 (PPh3)2 with Salicylaldehyde-2-hydroxy(mercapto)anil. Molecular Structure of Bis[salicylaldehyde-2-hydroxyanilato(2-)]rhenium(IV)
  13. Charge - Transfer Complexes of Metal Dithiolenes XXIV: Ion Pairs of the Tetrakis(dimethylamino)ethene Dication with Dithiolene Metalate Dianions
  14. Bis(trifluormethyl)disulfan und -trisulfan: Molekülgeometrie im festen Zustand [1] / Bis(trifluoromethyl)disulfane and Trisulfane: Molecular Geometry in the Solid State [1]
  15. 1,3-Dioxolane von N-substituierten 4-Piperidonen als Dehydrierungssubstrat / 1,3-Dioxolanes of N-Substituted 4-Piperidones as Substrates for Dehydrogenations
  16. Synthesis and Structure of Bis[di(methylcyclopentadienyl)chloro-titanium]trisulfide [(Cp′2ClTi)2S3] - a Reagent for Trisulfide Ligand Transfer Reactions [1]
  17. Ba(VO)4(AsO4)2(As2O7): Ein neues Divanadyl(IV)-Arsenat mit flächenverknüpften V2O8+1-Oktaederdoppeln / Ba(VO)4 (AsO4)2 (As2O7): A New Divanadyl(IV)-Arsenate Containing Face Shared V2O8+, Double Octahedra
  18. Über die Darstellung von CH3C6H4S(O)2NCl2H+SbF-6 und die Kristallstruktur von CH3C6H4S(O)2NCl2 / On the Synthesis of CH3C6H4S(O)2NCl2,H+SbF-6 and the Crystal Structure of CH3C6H4S(O)2NCl2
  19. Bis-und Tris[μ-nitrido-bis(diorganylphoshinato-O,O′)]- element( 1+)-Kationen / Bis- and Tris[μ-nitrido-bis(diorganylphosphinato-O,O′)]-element(1+) Cations
  20. Die Synthese und Kristallstruktur des Borat-Phosphats: α -Zn3(BO3)(PO4) / Synthesis and Crystal Structure of the Borate-Phosphate: α-Zn3(BO3)( PO4)
  21. Occurrence of Toxin Producing Cyanobacteria in Hungary. Isolation, Separation and Identification of Microcystins
  22. Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports
  23. Synthesis of Cationic Ruthenium Thioketene Complexes through Intramolecular 1,2-Elimination [1]
  24. Eindimensionale Kupfer(II)-Koordinationspolymere: Kristall-Engineering durch variable Verknüpfungsmuster [1] / One Dimensional Copper(II) Coordination Polymers: Crystal Engineering through Variable Types of Linkage [1]
  25. Darstellung und spektroskopische Charakterisierung von Trifluormethylazosulfonylmethan CH3S(O) 2NNCF3 / Preparation and Spectroscopic Characterization of Trifluoromethylazosulfonylmethan CH3S(O)2NNCF3
  26. Kristallstruktur von 1,1,1-Trichloro-cyclo-1λ6-wolframa-3,5-dithia-2,4,6- triazin, [WCl3(N3S2 )]2 / Crystal Structure of 1,1,1-Trichloro-cyclo- 1λ6-tungsta-3,5-dithia-2,4,6-triazine, [WCl3(N3S2)]2
  27. The Stannide Zr5CuSn3
  28. Die Kristallstruktur von Tris(trimethylstannyl) acetonitril / Crystal Structure of Tris(trimethylstannyl)- acetonitrile
  29. Die Kristallstrukturen von Trimethylbleiiodid und Diphenylbismutchlorid / Crystal Structures of Trimethyllead Iodide and Diphenylbismuth Chloride
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 11.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/znb-1997-0122/html
Scroll to top button