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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
Benzyl azide solution, ~0.5 M in dichloromethane, ≥95.0% (HPLC)
Sigma-Aldrich
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Imidazole, European Pharmacopoeia (EP) Reference Standard
Ondansetron impurity E, European Pharmacopoeia (EP) Reference Standard
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Methanol, puriss., meets analytical specification of Ph Eur, ≥99.7% (GC)
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Methanol, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.8% (GC)
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Imidazole, ReagentPlus®, 99%, Redi-Dri, free-flowing
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Imidazole, for molecular biology, ≥99% (titration), free-flowing, Redi-Dri
Supelco
Residual Solvent - Acetonitrile(solution in DMSO), Pharmaceutical Secondary Standard; Certified Reference Material
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Imidazole, ACS reagent, ≥99% (titration)
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Methylamine solution, 33 wt. % in absolute ethanol ((denatured with 1% toluene))
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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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Methylamine solution, 40 wt. % in H2O
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Trichloroacetic acid, ACS reagent, ≥99.0%
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Water, PCR Reagent
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Trichloroacetic acid, ≥99.0% (titration)
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E-Toxate Water, endotoxin, free
Supelco
Water, for HPCE, for luminescence, suitable for UV/Vis spectroscopy
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Water, Deionized
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Water, for molecular biology, sterile filtered