Macroporous oligonucleotide synthesis

Interest in highly cross-linked (20-30% DVB) macroporous polystyrene arose in the early days of oligonucleotide synthesis [158]. It has been argued that this type of support allows for faster reaction kinetics than the low cross-linked gel-type polystyrene. Modified with a trityl-type tinker, it has been tested by Roster and Cramer [159] in the phosphodiester method. The limitations of the chemistry hampered its use for oligomers longer than a few nucleotides. 

The most common trityl anchor was monomethoxytrityl (Figure 19.5), employed in the phosphodiester method on PS-1% DVB by Melby and Strobach [146], on macroporous PS by Roster and Cramer [159] and on PTFE grafted polystyrene by Potapov d. al. [167] A dimethoxytrityl linker was used by Roster and Cramer for the phosphodiester chemistry on popcorn PS [144] and by Belagaje and Brush [155] for their original adaptation of the phosphotriester method for the synthesis in 5 -to-3 direction (Figure 19.5). Roster has also described a trityl anchor linked to a silica gel support [185]. Similar linkers have been exploited for liquid-phase oligonucleotide synthesis (Section 19.4). 

The fact that macroporous, highly cross-linked polystyrene does not swell makes this support particularly interesting for continuous-flow synthesis in columns. This support has also been successfully used as an alternative to CPG for the solid-phase synthesis of oligonucleotides [90,91]. Furthermore, because reagents do not need to penetrate into the polystyrene network, enzyme-mediated reactions should also proceed smoothly on macroporous polystyrene [85]. 

The solid-phase synthesis of oligonucleotides by the phosphoramidite approach requires the use of a solid support that is functionalized with an appropriate nucleoside. Solid supports are typically macroporous structures... 

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