An expedient process for reducing the formation of process-related impurities during solid-phase synthesis of potential nucleic acid-based drugs.

With the intent of mitigating the formation of process-related impurities during solid-phase synthesis of DNA or RNA sequences, a hydroxylated controlled-pore glass support conjugated to three, five or seven hexaethylene glycol spacers was prepared and demonstrated to provide a more efficient and robust synthesis process. Indeed, the use of a support conjugated to five hexaethylene glycol spacers led to a 19% up to 42% reduction of process-related impurities contaminating synthetic nucleic acid sequences, when compared to that obtained from the same DNA/RNA sequences synthesized using a commercial long-chain alkylamine controlled-pore glass support under highly similar conditions.