Multiple oligonucleotide synthesis in tandem on solid-phase supports for small and large scale synthesis.

Multiple oligonucleotides linked end-to-end in tandem can be synthesized by adding a nucleoside to the 5'-OH end of a prior sequence. Nucleosides with 3'-succinyl or Q-Linker arms are coupled with HBTU/DMAP. Alternatively, new phosphoramidite reagents with 3'-ester linkages can be used. Hydroxyl or amino supports can also be used as universal starting materials. Treatment with NH4OH cleaves the 3'-ester to yield only 3'-OH groups and no unwanted 3'-phosphorylated products occur.