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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

Acetonitrile, analytical standard

Supelco

N,N-Dimethylacetamide, analytical standard

Sigma-Aldrich

2-Hydroxybutyric acid sodium salt, 97%

Sigma-Aldrich

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

Sigma-Aldrich

Water-¹⁶O, ≥99.94 atom % ¹⁶O

Sigma-Aldrich

Citric acid, ACS reagent, ≥99.5%

Supelco

Acetic anhydride, derivatization grade (GC derivatization), LiChropur^™, ≥99.0%

Supelco

Dichloromethane, analytical standard

Sigma-Aldrich

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

Sigma-Aldrich

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

Supelco

Pyridine, analytical standard

Sigma-Aldrich

Citric acid, ≥99.5%, FCC, FG

Sigma-Aldrich

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

Sigma-Aldrich

N,N-Dimethylacetamide-d₉, 99 atom % D

Sigma-Aldrich

Acetic anhydride, ACS reagent, ≥98.0%

Sigma-Aldrich

2,6-Dimethylpyridine, ≥99%

Sigma-Aldrich

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

Sigma-Aldrich

Pyridine, anhydrous, 99.8%

Sigma-Aldrich

N,N-Dimethylacetamide, anhydrous, 99.8%

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%

Sigma-Aldrich

Acetic anhydride, 99.5%

Sigma-Aldrich

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

Sigma-Aldrich

Citric acid, 99%

Sigma-Aldrich

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

Sigma-Aldrich

Trichloroacetic acid solution, 6.1 N

Supelco

Dichloromethane, Selectophore^™, ≥99.5%

Sigma-Aldrich

Acetic anhydride, ReagentPlus^®, ≥99%

Sigma-Aldrich

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

Sigma-Aldrich

Ultrapure Acetonitrile

Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard