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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, ACS reagent, ≥99.0%

Sigma-Aldrich

Citric acid, anhydrous, free-flowing, Redi-Dri^™, ACS reagent, ≥99.5%

Sigma-Aldrich

N,N-Dimethylacetamide, spectrophotometric grade, ≥99%

Sigma-Aldrich

Pyridine, ReagentPlus^®, ≥99%

Sigma-Aldrich

Acetonitrile, ReagentPlus^®, 99%

Sigma-Aldrich

Iodine, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.8-100.5%

SAFC

N,N-Dimethylacetamide, Ph. Eur.

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ special grade

Sigma-Aldrich

Citric acid, SAJ first grade, ≥99.5%

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

Sigma-Aldrich

Acetonitrile, JIS special grade, ≥99.5%

Sigma-Aldrich

Acetonitrile, SAJ first grade, ≥99.0%

Sigma-Aldrich

Acetonitrile, ≥99.8%, suitable for HPLC

Sigma-Aldrich

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

Supelco

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

Sigma-Aldrich

Trichloroacetic acid solution, 6.1 N

Sigma-Aldrich

Iodine, 99.999% trace metals basis

Sigma-Aldrich

Citric acid, ACS reagent, ≥99.5%

Supelco

Acetonitrile, HPLC grade, ≥99.93%

Sigma-Aldrich

Acetic anhydride, JIS special grade

Sigma-Aldrich

Acetic anhydride, ACS reagent, ≥98.0%

Sigma-Aldrich

N,N-Dimethylacetamide-d₉, 99 atom % D

Sigma-Aldrich

Iodine, anhydrous, beads, −10 mesh, 99.999% trace metals basis

Sigma-Aldrich

Pyridine, anhydrous, 99.8%

Sigma-Aldrich

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

Sigma-Aldrich

Acetonitrile, ≥99.5%, ACS reagent

Sigma-Aldrich

Iodine, ≥99.99% trace metals basis

Sigma-Aldrich

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

Supelco

Pyridine, analytical standard

Supelco

N,N-Dimethylacetamide, analytical standard