Abstract
Abstract A new sulfurizing reagent has been developed for the automated synthesis of phosphorothioate oligonucleotides 1 via the phosphoramidite method. Tetraethylthiuram disulfide (TETD) converts internucleotide cyanoethyl phosphite 2 to the phosphorothioate triester 3 within 15 minutes at room temperature after each coupling step. With an optimized synthesis cycle, the efficiency of phosphorothioate oligonucleotide synthesis is comparable to that of phosphodiester oligonucleotides. Large scale synthesis (200μmole), oligonucleotides up to 100 bases long, and mixed phosphorothioate/phosphodiester DNA are demonstrated.
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