Group is more novel and the support that exhibited the most desirable features fell into this category. Support (5) was tested with CPG (5a) and polystyrene (5b) as the core particles. Universal support (5) proved to be the only truly universal support in that it was used successfully for the production of short and long DNA oligomers, as well as for the production of biologically active siRNA. INTRODUCTION Standard oligonucleotide synthesis uses a solid support that contains the first nucleoside covalently bound to the support by a linker that is hydrolyzed during the cleavage step following solid-phase synthesis. This support-bound nucleoside becomes the 3′-terminal residue of the final oligonucleotide after the cleavage and deprotection steps. Clearly, this approach requires the use of at least four solid supports for general DNA synthesis along with an additional four supports for RNA synthesis. Various solid supports containing unusual nucleosides for specific applications are also required. A universal support does not have the intended 3′-nucleoside attached. Rather, the 3′-nucleoside or residue is added in the first cycle, generating an undesired phosphate linkage between this nucleoside and the universal support. This approach requires that this phosphate linkage be removed during the cleavage and/or deprotection steps. However, the universal support strategy offers the following clear advantages: (i) eliminates the possibility of errors in parallel synthesis applications where up to 384 wells may contain different supports; (ii) eliminates the need for at least four supports for DNA synthesis and four supports for RNA synthesis; (iii) simplifies the preparation of oligonucleotides with modified or unusual nucleosides at the 3′-terminus. UNIVERSAL SUPPORTS Several universal supports have been described in the literature1-5 and a selection of these is now commercially available. The structures of a selection of the commercially available supports are shown in Figures 1 and 2. These supports fall into two categories, as follows, depending on the timing of the dephosphorylation step that generates the 3’hydroxyl of the target oligonucleotide.
Cleavage THEN Deprotection and Dephosphorylation
In the first category, the regular cleavage step of oligonucleotide synthesis predominantly leaves intact the residue or tether attached to the 3′-nucleoside through a phosphodiester linkage.
The dephosphorylation step along with elimination of the unwanted tether takes place during the deprotection step and usually requires stronger conditions than normal deprotection.301326-22-7 References These universal supports1 are either non-nucleosidic but incorporating a 5-membered ring similar to the ribose ring found in nucleosides or nucleoside-based supports, or protected nucleosides configured for base-mediated elimination.471905-41-6 Formula Examples of these supports are shown in Figure 1.PMID:22855962
Cleavage by Dephosphorylation THEN Deprotection
Figure 1. Universal Supports – Dephosphorylation after Cleavage
In the second group, the dephosphorylation step is the cleavage step and the only oligonucleotides released into solution already have a 3′-hydroxyl group. Further conventional deprotection leads to the fully deprotected oligonucleotide. The first example4 of this type of support uses a nucleotide attached to the support by a non-cleavable linker. The second example5 is a novel non-nucleosidic support. Examples of these supports are shown in Figure 2.
RNA Synthesis
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