A 'catch and release' strategy towards HPLC-free purification of synthetic oligonucleotides by a combination of the strain-promoted alkyne-azide cycloaddition and the photocleavage.

A convenient strategy to purify oligonucleotides (ONs) synthesized by solid phase synthesis on an automatic DNA/RNA synthesizer was described. By attaching a photocleavable azide linker as the last phosphoramidite unit in the ON synthesis, only the desired full-length sequence was 'caught' on a controlled pore glass (CPG) resin possessing an aza-dimethoxycyclooctyne (DIBAC) derivative. Washing the resulting CPG resin to remove all unbounded species, the subsequent photoirradiation allowed the pure ONs to be 'released' without leaving any chemical modifications on native ON structure or chemical reagents from the solid phase ON synthesis.