A method for purifying an oligonucleotide that comprises providing an oligonucleotide
attached to a substrate, wherein the oligonucleotide contains phosphate protecting
groups; contacting the oligonucleotide with a reagent, e.g., an organic amine,
that cleaves the phosphate protecting groups from the oligonucleotide without detaching
the oligonucleotide from the substrate; isolating the oligonucleotide attached
to the substrate from the cleaved phosphate protecting groups; and cleaving the
oligonucleotide from the substrate. This method provides crude oligonucleotide
mixtures that are easier to purify and from which the desired full-length oligonucleotide
product can be isolated in higher yields.
