Universal Synthesis

Universal Synthesis

Universal supports are advantageous when there is no nucleobase or modification already present or when a 3’-modification support is unavailable—and it helps simplify your supply chain.

A 'universal' support in the context of oligonucleotide synthesis is a solid support, normally CPG, where no functionality (e.g. nucleobase or modification) of the support is retained at the 3' end of the oligo sequence after cleavage.

There are advantages in using a ‘universal’ support where there is no nucleobase or modification already present (e.g. when using plate synthesizer).

• In this case, the first base at the 3'-end is determined by the first phosphoramidite addition in the synthesis cycle. 
• When preparing wells in plate synthesizers this eliminates the possibility of the incorrect resin being placed in a well. 
• It also allows automated preparation of the plates to stock ready for synthesis. 
• There is an added benefit in large-scale syntheses, where the supply chain is simplified as only the one support is required.

A universal support can also be applied in situations where a 3'-modification support is not available, using a phosphoramidite modifier as the first addition in the cycle (this will only work with phosphoramidites capable of extending the oligo chain, i.e. not 5'-modifiers, and which are compatible with the universal support cleavage and deprotection conditions).

Although we still offer the original McLean 'universal' support, and a Q-linker version, our most effective product for universal synthesis is the Unprotected Universal Solid Support with a labile N-iPr linker*. It is similar in structure to the N-Ph product developed at Isis Pharmaceuticals as UnyLinker™. The advantage of the N-iPr version is that the removal of the linker from the 3'-terminus of synthetic oligonucleotides occurs about 5 times more rapidly.

The advantage of the unprotected ('DMT-off') universal supports over the respective DMT-protected supports is that no linker is cleaved from the solid support during the initial detritylation step. With DMT-protected supports, 10 to 25% of the linker is cleaved off during this step thus reducing the loading and the yield of oligonucleotides.

Further, this eliminates the need for an initial detritylation step. The DMT group in Universal supports is more stable than in nucleosidic supports by a factor of 5 to 7. When using DMT-protected supports, therefore, the user is required to create a custom detritylation protocol for the initial detritylation. This requirement is removed by using our DMT-off product.

*This product is distributed on behalf of AM Chemicals LLC.