The present invention discloses improved methods for oligonucleotide
synthesis and purification. In the methods of the invention, a half-life
is determined for deprotection of the 5'-OH protecting group at the
5'-terminus of an oligonucleotide post-synthesis. The half-life is used to
determine an optimal reaction time for removal of the 5'-OH protecting
group. The methods of the invention are amenable to the large-scale
synthesis and purification of oligonucleotides.