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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

Acetonitrile, for residue analysis, JIS 5000

Sigma-Aldrich

Acetonitrile, for chromatography

Sigma-Aldrich

Acetic anhydride, JIS special grade

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ special grade

Supelco

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

Sigma-Aldrich

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

Sigma-Aldrich

Dichloromethane, JIS special grade, ≥99.0%

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

Sigma-Aldrich

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

Sigma-Aldrich

Pyridine, JIS special grade, ≥99.5%

Sigma-Aldrich

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

Sigma-Aldrich

Citric acid, SAJ first grade, ≥99.5%

Sigma-Aldrich

Pyridine, suitable for hydroxyl value determination, ≥99.5%

Sigma-Aldrich

Acetonitrile, JIS special grade, ≥99.5%

Sigma-Aldrich

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

Sigma-Aldrich

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

Sigma-Aldrich

Methanol solution, NMR reference standard, 4% in methanol-d₄ (99.8 atom % D), NMR tube size 3 mm × 8 in.

Supelco

Acetonitrile, HPLC grade, ≥99.93%

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

Sigma-Aldrich

Trichloroacetic acid solution, 6.1 N

Sigma-Aldrich

2-Hydroxybutyric acid sodium salt, 97%

Supelco

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

Sigma-Aldrich

Citric acid, 99%

Supelco

Acetic anhydride, for GC derivatization, LiChropur^™, ≥99.0%

Sigma-Aldrich

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

Sigma-Aldrich

Pyridine, ≥99%

Sigma-Aldrich

Acetic anhydride, ACS reagent, ≥98.0%

Sigma-Aldrich

2,6-Dimethylpyridine, ≥99%

Supelco

Pyridine, analytical standard

Supelco

Dichloromethane, Selectophore^™, for ion-selective electrodes, ≥99.5%