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1997 (1)
1Author    Michael Gerster, Martin Maier, Nils Clausen, Jens Schewitz, Ernst BayerRequires cookie*
 Title    Optimized Large Scale Synthesis of Phosphorothioate Oligonucleotides on PS-PEG Supports  
 Abstract    Sulphurization is a crucial step during synthesis of phosphorothioate oligonucleotides. Insuf­ ficient 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 //mol) 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 phos­ phodiester 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. 
  Reference    (Z. Naturforsch. 52b, 110—116 [1997]; received September 11 1996) 
  Published    1997 
  Keywords    Large Scale Synthesis, Oligonucleotide Phosphorothioate, PS-PEG, Sulphurizing Reagent 
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 TEI-XML for    default:Reihe_B/52/ZNB-1997-52b-0110.pdf 
 Identifier    ZNB-1997-52b-0110 
 Volume    52