STUDIES ON POLYNUCLEOTIDES .93. A FURTHER STUDY OF SYNTHESIS OF DEOXYRIBOPOLYNUCLEOTIDES USING PREFORMED OLIGONUCLEOTIDE BLOCKS

In a further study of polynucleotide synthesis by the use of preformed oligonucleotide blocks, the condensation between the hexanucleotide Tr-TpTpTpTpTpT and the thymidine di-, tri-, tetra-, and pentanucleotides carrying 5ʹ-phosphate end groups (pTpT-OAc and homologs) has been investigated. Mesitylenesulfonyl chloride was used as the condensing agent. The molar excess of the oligonucleotide blocks bearing phosphomonoester groups, the proportion of the condensing agent, and the reaction time were varied. The rates of condensation reaction as well as the isolated yields of the desired products were determined. In addition, attention was paid to the extent of polynucleotide chain degradation during the activation process and the nature of the resulting side products. The use of a 10:1 ratio of the oligonucleotide block to Tr-T6P5, a lower amount of the condensing agent, and shorter reaction times than those used previously gave the best yields with minimal side reactions. The condensations using di- and trinucleotide blocks showed almost the same rate, and the optimal yields of the desired polynucleotides were, respectively, 78 and 75%. The condensations using the tetra- and pentanucleotides also proceeded at about the same rate, but this rate was lower than that observed for the di- and trinucleotide reactions; the maximum yields obtained in these condensations were close to 50%. © 1969, American Chemical Society. All rights reserved.