Details

Autor(en) / Beteiligte

• Krotz, Achim H
• McElroy, Bethany
• Scozzari, Anthony N
• Cole, Douglas L
• Ravikumar, Vasulinga T

Titel

Controlled Detritylation of Antisense Oligonucleotides

Ist Teil von

• Organic process research & development, 2003-01, Vol.7 (1), p.47-52

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2003

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 t 1/2 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.