Nucleoside dimers, methods of making and use in DNA synthesis

Abstract

The application provides a nucleoside dimer, a preparation method thereof and application in DNA synthesis. The nucleoside dimer of the application adopts a mixed skeleton of methyl phosphate and beta-cyanoethyl phosphoramidite, a new preparation method of the nucleoside dimer is obtained by optimizing a synthesis method and a purification process, and a foundation for high-quality DNA synthesis is laid. On this basis, the nucleoside dimer with the new skeleton is applied to DNA synthesis, an oligonucleotide fragment synthesis method suitable for the dimer is established, and an oligonucleotide fragment with a length of 100 nt is synthesized. Fidelity experiment shows that the error rate of the DNA fragment synthesized by using the dimer is only 3.75 errors / Kb, and high-fidelity DNA synthesis is realized. The preparation method of the nucleoside dimer with the new skeleton can realize large-scale and high-purity preparation, the nucleoside dimer can play an important role in improving the length and fidelity of oligonucleotide synthesis, and has practical value.

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