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Characterization of high molecular weight impurities in synthetic phosphorothioate oligonucleotides.
TLDR
Phosphorothioate oligonucleotides manufactured by standard phosphoramidite techniques using 2'-deoxyadenosine- or 2'-O-(2-methoxyethyl)-5-methylcytosine-loaded solid supports contain branched impurities, but these impurities are not produced when a universal, non-nucleoside derivatized support is used. Expand
Synthesis of High-Quality Antisense Drugs. Addition of Acrylonitrile to Phosphorothioate Oligonucleotides: Adduct Characterization and Avoidance
It is demonstrated that the acrylonitrile (AN) generated during the ammonolysis step of oligonucleotide manufacture selectively adds to thymine residue present in ISIS 2302 to give a full-lengthExpand
Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine.
TLDR
It is found that for the beta-anomer of AP, the complex between (AP)6T6and the target site G6A6*T6C6 is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 microM at pH 5.0, in contrast to 50 microM C6T 6 which has no effect on the cleavage pattern. Expand
Use of the 1-(2-fluorophenyl)-4-methoxypiperidin-4-yl (Fpmp) and related protecting groups in oligoribonucleotide synthesis: stability of internucleotide linkages to aqueous acid.
TLDR
It is concluded that Fpmp is a suitable 2'-protecting group even in the synthesis of particularly acid-sensitive sequences as it is demonstrated that the rate of acid-catalyzed hydrolysis of the internucleotide linkages of oligoribonucleotides is sequence dependent. Expand
Formation of 4,4'-dimethoxytrityl-C-phosphonate oligonucleotides.
Incomplete sulfurization during solid-phase synthesis of phosphorothioate oligonucleotides using phosphoramidite chemistry was identified as the cause of formation of two new classes ofExpand
Pyridinium Trifluoroacetate/N-Methylimidazole as an Efficient Activator for Oligonucleotide Synthesis via the Phosphoramidite Method
A new activator is reported for coupling phosphoramidites to a free 5‘-hydroxyl group during oligonucleotide synthesis. Pyridinium trifluoroacetate/N-methyl imidazole is a remarkably efficientExpand
Efficient triple helix formation by oligodeoxyribonucleotides containing alpha- or beta-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues.
TLDR
Molecular modelling studies showed that an alpha-anomeric AP nucleotide can be accommodated within an otherwise beta-anomersic triplex with only minor perturbation of the triplex structure, and the lack of a differential stability between alpha-AP- and beta- AP-containing triplexes at pH >7, predicted from the behaviour of the B- type models, suggests that the A-type models are more appropriate. Expand
Synthesis of Antisense Oligonucleotides: Replacement of 3H-1,2-Benzodithiol-3-one 1,1-Dioxide (Beaucage Reagent) with Phenylacetyl Disulfide (PADS) As Efficient Sulfurization Reagent: From Bench to
It is demonstrated that phosphorothioate oligodeoxyribonucleotides can be synthesized on scales from 1 μmol to 150 mmol using phenylacetyl disulfide (PADS) as an efficient and economical replacemen...
Impurities in Oligonucleotide Drug Substances and Drug Products.
TLDR
Reporting, identification, and qualification thresholds suitable for product-related impurities of therapeutic oligonucleotides are proposed and chemistry and safety aspects are considered. Expand
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