Extremely high purity oligonucleotides and methods of synthesizing them using dimer blocks

作者: Jose Gonzalez , Warren E. Schwartz , Jin-Yan Tang , Nandkumar Bongle

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摘要: The present invention comprises an improved method of synthesizing oligonucleotides. employing dinucleotides (or "dimer blocks") as the basic synthetic unit building block. results in extremely high purity oligonucleotides which N-1 content is very low, generally less than 1-2% full length, N, oligonucleotide. We have found that synthesis using dinucleotide phosphorothioates having little phosphodiester content. Furthermore, we amount dimer required each coupling step can be about 6 and preferably 2 equivalents. Synthesis according to block approach described herein also conducted without capping has heretofore been deemed necessary after coupling.

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