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  • High-throughput chemical modification of oligonucleotides for systematic structure-activity relationship evaluation.

High-throughput chemical modification of oligonucleotides for systematic structure-activity relationship evaluation.

Bioconjugate chemistry (2014-11-15)
Daniel Zewge, Francis Gosselin, Denise M Kenski, Jenny Li, Vasant Jadhav, Yu Yuan, Sandhya S Nerurkar, David M Tellers, W Michael Flanagan, Ian W Davies
ABSTRACT

Chemical modification of siRNA is achieved in a high-throughput manner (96-well plate format) by copper catalyzed azide-alkyne cycloadditions. This transformation can be performed in one synthetic operation at up to four positions with complete specificity, good yield, and acceptable purity. As demonstrated here, this approach extends the current synthetic options for oligonucleotide modifications and simultaneously facilitates the systematic, rapid biological evaluation of modified siRNA.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Methanol, NMR reference standard
Sigma-Aldrich
Benzyl azide solution, ~0.5 M in dichloromethane, ≥95.0% (HPLC)
Imidazole, European Pharmacopoeia (EP) Reference Standard
Ondansetron impurity E, European Pharmacopoeia (EP) Reference Standard
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Imidazole, ACS reagent, ≥99% (titration)
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Methylamine solution, 40 wt. % in H2O
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Triethylamine, for amino acid analysis, ≥99.5% (GC)
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Triethylamine, BioUltra, ≥99.5% (GC)
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Methanol, anhydrous, 99.8%
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Methylamine solution, 2.0 M in methanol
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Methylamine solution, 2.0 M in THF
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Azidomethyl phenyl sulfide, 95%
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Trichloroacetic acid, ACS reagent, ≥99.0%
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Trichloroacetic acid, ≥99.0% (titration)
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Methylamine solution, 33 wt. % in absolute ethanol ((denatured with 1% toluene))
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Water, ACS reagent, for ultratrace analysis
Pure Water Density Standard, UKAS ISO/IEC17025 and ISO Guide 34 certified, density: 0.9982 g/mL at 20 °C, density: 0.9970 g/mL at 25 °C
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Methanol, Laboratory Reagent, ≥99.6%
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Methanol, suitable for HPLC, ≥99.9%
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Methanol, HPLC Plus, ≥99.9%
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Methanol, Absolute - Acetone free
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2,6-Lutidine, analytical standard
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Methanol, Pharmaceutical Secondary Standard; Certified Reference Material
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Methanol, ACS spectrophotometric grade, ≥99.9%
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Methanol, analytical standard
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E-Toxate Water, endotoxin, free
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Water, for HPCE, for luminescence, suitable for UV/Vis spectroscopy
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Water, Deionized