The key step in the use of any universal support in oligonucleotide synthesis is the dephosphorylation of the 3'-phosphate group to form the desired 3'-hydroxyl group. Universal Support III makes use of a novel (±)-3-Amino-1,2-propanediol linker that takes advantage of an amide group's ability to form weak hydrogen bonds leading to an amide assisted dephosphorylation under mildly basic conditions, typically 0.2M anhydrous ammonia in methanol in 20 minutes. The amide assisted dephosphorylation reaction eliminates the desired 3’- OH oligonucleotide into solution while the product of any β-elimination competing side reaction remains bound to the support. Typically, greater than 95% yield of product oligonucleotide is achieved.
After cleavage and dephosphorylation with anhydrous ammonia in methanol, standard deprotection using the conditions appropriate for removal of the protecting groups on the nucleobases is then used to generate the oligonucleotides.
This product is covered by US Patent No.: 6,770,754 and European Patent No.: 1404695.