The present invention relates to improved methods for the preparation of
nucleic acids. More particularly, conventional solid supports used for
nucleic acid synthesis are derivatized with activators having pKas within
the 4 to 7 range. Preferentially, CPG-based solid supports are reacted
with trialkoxysilanes containing an activator moiety such as pyridine.
During each deblocking step of the nucleic acid synthesis cycle, bound
pyridiniums are generated, yielding a weak acidic medium spreads
throughout the solid support. The bound activators efficiently activate
the phosphoramidite reagents towards coupling with 5'-hydroxynucleosides
bound to the solid supports, thus eliminating or supplementing external
deliveries of activator during the coupling steps.