Both DNA and RNA synthesis is based on the solid-phase synthesis strategy and phosphoramidite chemistry, a DNA synthesizer could be used to synthesize RNA or RNA analogues without further modification, and the reagents in DNA synthesis could be used directly in RNA and artificial nucleic acids' synthesis. As shown in Figure 1, the 2'-hydroxy in RNA phosphoramidite is protected with silyl protective group, i.e. t-butyldimethylsilyl (TBDMS), preventing the side reactions on fragile 2'-hydroxy group. The bulky TBDMS group hindered the reaction between phosphoramidite and the 5'-hydroxy group on the solid support, and a longer coupling time is required to realize the satisfy the coupling efficiency.
Similar as DNA synthesis, the synthesized RNA was first cleavaged from the solid support by aminolysis, then the TBDMS group was cleavaged by tetrabutylammonium fluoride (TBAF) or trimethylamine trihydrofluoride. Crude RNA could be purified by recrystallized from alcohol and HPLC.
Figure 1. The chemical structure of basic building blocks in DNA and RNA synthesis.
a) dABz phosphoramidite and b) rABz 2'-OTBDMS phosphoramidite.
The development of siRNA drug requires the structure analogues of native RNA to increase the biocompatibility, the 2'-hydroxy on RNA could be replaced by MeO, F and MOE group, and the locked nucleic acid (LNA) also give good performance in RNA therapy (Figure 2). These phosphoramidites give similar actives as DNA type phosphoramidites in the synthesis, and the work-up and purification process of these non-natural nucleic acids is similar as the native DNA.
Figure 2. The chemical structure of building blocks in siRNA drugs. a) dABz 2-MeO phosphoramidite; b) dABz 2-F phosphoramidite; c) dABz 2-MOE phosphoramidite and d) dABz Locked phosphoramidite.
Phosphoramidites are essential for the synthesis of genes, including mainly the DNA and RNA families and their derivatives, all phosphoramidite above we can offer in a package.
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Post time: Aug-09-2022