UnyLinker dimer impurity characterization and process improvement |
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| Authors: | Joshua L. Brooks Phil Olsen Lijian Chen Andrew A. Rodriguez |
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| Affiliation: | Ionis Pharmaceuticals, 2855 Gazelle Court, Carlsbad, CA 92010, United States |
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| Abstract: | Herein, we describe the isolation and characterization of a UnyLinker dimer which, if left uncontrolled, can become incorporated in oligonucleotide products. The dimer is formed as a result of an unusual intermolecular osmium-catalyzed etherification. We demonstrate that by simply replacing H2O2 as the co-oxidant with NMO, none of the UnyLinker dimer impurity is formed. |
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| Keywords: | Oligonucleotide Dihydroxylation UnyLinker Dimerization |
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