Polyethylene glycol |
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Authors: | Gian Maria Boora |
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Affiliation: | (1) Department of Organic Chemistry, Biopolymer Research Center, C.N.R., University of Padova, Padova, Italy;(2) Present address: Department of Pharmaceutical, Chemical, and Technological Sciences, University of Cagliari, Italy |
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Abstract: | The increasing demand of synthetic oligonucleotides for therapeutic and diagnostic purposes can be hardly satisfied by simply upscaling the commercial synthesizers. The introduction of a liquid-phase method that utilizes a polymeric support soluble into the reaction media can overcome the shortcomings related to the heterogeneity of the solid phase and allow a convenient large-scale process. Recently we have proposed a new synthetic approach for the oligonucleotide production that utilizes polyethylene glycol or PEG as soluble supporting polymer. We call this method High-Efficiency Liquid Phase or HELP. This approach preserves the advantages of a homogeneous synthesis in solution and adds an easy purification step of all the intermediates, mimicking the solid-phase procedure. In fact, reagent excess and byproducts can be eliminated by a simple precipitation-and-filtration step at the end of each synthetic cycle. Since all the reactions take place in solution, the scale-up of the process is easily predictable. Various synthetic protocols have been tested and optimized for the oligonucleotide production, up to the antisense-size level. After the phosphotriester and the phosphoramidite chemistry, the H-phosphonate approach is now under development. The possibility of an efficient automation of the whole process is also investigated. |
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Keywords: | Oligonucleotides, synthesis of solid-phase synthesis liquid-phase synthesis polyethylene glycol PEG polymer-supported chemistry synthesizers phosphotriesters phosphor-amidites H-phosphonates |
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