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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

Supelco

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

Sigma-Aldrich

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

Sigma-Aldrich

Pyridine, JIS special grade, ≥99.5%

Sigma-Aldrich

Dichloromethane, JIS special grade, ≥99.0%

Sigma-Aldrich

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

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

Acetonitrile, ≥99.8%, suitable for HPLC

Sigma-Aldrich

Acetonitrile, SAJ first grade, ≥99.0%

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

Sigma-Aldrich

Methanol-¹²C, 99.95 atom % ¹²C

Sigma-Aldrich

Acetonitrile, for residue analysis, JIS 5000

Sigma-Aldrich

Acetic anhydride, JIS special grade

Sigma-Aldrich

Acetic anhydride, 99.5%

Sigma-Aldrich

Dichloromethane, anhydrous, ≥99.8%, contains 40-150 ppm amylene as stabilizer

Sigma-Aldrich

Methylamine, anhydrous, ≥98%

Sigma-Aldrich

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

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ special grade

Sigma-Aldrich

Citric acid, 99%

Sigma-Aldrich

Citric acid, BioUltra, anhydrous, ≥99.5% (T)

Supelco

N,N-Dimethylacetamide, analytical standard

Supelco

Acetonitrile, analytical standard

Supelco

Pyridine, analytical standard

Sigma-Aldrich

Citric acid, anhydrous, suitable for cell culture, suitable for plant cell culture

Sigma-Aldrich

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

Sigma-Aldrich

Iodine, ≥99.99% trace metals basis

Sigma-Aldrich

2-Hydroxybutyric acid sodium salt, 97%

Supelco

Dichloromethane, ≥99.9%