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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

Pyridine, JIS special grade, ≥99.5%

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ first grade, ≥99.0%

Sigma-Aldrich

Acetonitrile, ≥99.8%, for residue analysis, JIS 1000

Sigma-Aldrich

Pyridine, suitable for hydroxyl value determination, ≥99.5%

Sigma-Aldrich

Acetonitrile, JIS special grade, ≥99.5%

Sigma-Aldrich

Acetonitrile, ≥99.8%, suitable for HPLC

Sigma-Aldrich

Acetonitrile, SAJ first grade, ≥99.0%

Sigma-Aldrich

Dichloromethane, JIS special grade, ≥99.0%

Sigma-Aldrich

Citric acid, SAJ first grade, ≥99.5%

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

Sigma-Aldrich

Acetonitrile, ≥99.8%, for residue analysis, JIS 300

Sigma-Aldrich

Acetic anhydride, Arxada quality, ≥99.5% (GC)

Sigma-Aldrich

Trichloroacetic acid solution, 6.1 N

Sigma-Aldrich

2-Hydroxybutyric acid sodium salt, 97%

Sigma-Aldrich

Citric acid, ACS reagent, ≥99.5%

Supelco

Dichloromethane, ≥99.9%

Sigma-Aldrich

Iodine, 99.999% trace metals basis

Sigma-Aldrich

N,N-Dimethylacetamide, ReagentPlus^®, ≥99%

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles

Supelco

Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material

Supelco

Dichloromethane solution, contains 10 % (v/v) methanol

Sigma-Aldrich

Dichloromethane, suitable for HPLC, ≥99.9%, contains 40-150 ppm amylene as stabilizer

Supelco

Acetonitrile, HPLC grade, ≥99.93%

Sigma-Aldrich

N,N-Dimethylacetamide-d₉, 99 atom % D

Sigma-Aldrich

Acetic anhydride, 99.5%

Sigma-Aldrich

Citric acid, ≥99.5%, FCC, FG

Sigma-Aldrich

N,N-Dimethylacetamide, suitable for peptide synthesis, ≥99.8% (GC)

Sigma-Aldrich

Pyridine, ≥99%

Sigma-Aldrich

Acetic anhydride, ReagentPlus^®, ≥99%

Sigma-Aldrich

2,6-Dimethylpyridine, ≥99%