Autor: |
Krotz, A. H., McElroy, B., Scozzari, A. N., Cole, D. L., Ravikumar, V. T. |
Zdroj: |
Organic Process Research & Development; January 2003, Vol. 7 Issue: 1 p47-52, 6p |
Abstrakt: |
The last chemical step in standard oligonucleotide synthesis, the acid-catalyzed removal of 4,4-dimethoxytrityl (DMTr) protecting groups from the 5-terminus of oligonucleotides is accompanied by hydrolysis of purine nucleoside glycosidic linkages (depurination). A mild procedure for controlled DMTr removal using NaOAc (10 mM, pH 3.0) under a fixed set of conditions has been developed. The calculation of the reaction time is based on a t1/2 versus pH profile, specifically determined for each individual oligonucleotide sequence. The effect of various solvent components on the reaction kinetics has been evaluated. As a result, oligonucleotides with improved impurity profile are obtained consistently from laboratory scale to production scale. |
Databáze: |
Supplemental Index |
Externí odkaz: |
|