Use of a Derivatized Merrifield Resin for the Polymer-Supported Synthesis of Oligodeoxyribonucleotides

Abstract

Commercial Merrifield resin was derivatized into a resin bearing acyl chloride groups. The derivatized resin can be linked to the 5'-hydroxyl group of thymidine via an acyl ester linkage. The polymer-supported thymidine gave thymidylylthymidine in a good yield on reaction with 3'-O-acetylthymidine 5'-phosphate in the presence of mesitylene sulfonyl chloride. When the polymer-supported thymidine was reacted with thymidine 5'-phosphate in the presence of dicyclohexylcarbodiimide, polymerization of thymidylic acid took place and polymer-supported oligothymidylic acid was obtained. The oligonucleotides were liberated from the resin by treatment with ammonia. It was found that this oligonucleotide mixture was composed exclusively of oligomers of the type, Tp (Tp)_nT. Oligomers up to the hexamer were purified and identified. This procedure would be convenient for the preparation of oligodeoxyribonucleotides of the general formula, X (pY)_n.