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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
N,N-Dimethylacetamide, ReagentPlus®, ≥99%
Sigma-Aldrich
Acetic anhydride, ACS reagent, ≥98.0%
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2,6-Dimethylpyridine, ≥99%
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Citric acid, ACS reagent, ≥99.5%
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2-Hydroxybutyric acid sodium salt, 97%
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Methanol-12C, 99.95 atom % 12C
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Acetic anhydride, Arxada quality, ≥99.5% (GC)
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Trichloroacetic acid solution, 6.1 N
Supelco
Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material
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Acetonitrile, electronic grade, 99.999% trace metals basis
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Citric acid, anhydrous, suitable for cell culture, suitable for plant cell culture
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Citric acid, 99%
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Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer
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N,N-Dimethylacetamide, anhydrous, 99.8%
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Acetic anhydride, 99.5%
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Imidazole buffer Solution, BioUltra, 1 M in H2O
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Pyridine, anhydrous, 99.8%
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Pyridine, ≥99%
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Acetic anhydride, ReagentPlus®, ≥99%
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Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer
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N,N-Dimethylacetamide-d9, 99 atom % D
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Acetonitrile, anhydrous, 99.8%
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Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))
SAFC
N,N-Dimethylacetamide, Ph. Eur.
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard
USP
Citric acid, United States Pharmacopeia (USP) Reference Standard
Supelco
Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material
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Pyridine, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard