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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
Dichloromethane, analytical standard
Supelco
Acetic anhydride, for GC derivatization, LiChropur, ≥99.0%
USP
Methyl alcohol, United States Pharmacopeia (USP) Reference Standard
USP
Citric acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Methanol solution, (Methanol:Dimethyl sulfoxide 1:1 (v/v))
Sigma-Aldrich
Acetic anhydride, Arxada quality, ≥99.5% (GC)
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, ReagentPlus®, 99%
Supelco
Iodine, ReagentPlus®, ≥99.8% (titration)
Sigma-Aldrich
Iodine, ACS reagent, ≥99.8%, solid
Sigma-Aldrich
N,N-Dimethylacetamide, spectrophotometric grade, ≥99%
Sigma-Aldrich
Pyridine, ReagentPlus®, ≥99%
Sigma-Aldrich
Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%
Sigma-Aldrich
N,N-Dimethylacetamide, ReagentPlus®, 99%
Sigma-Aldrich
Citric acid, meets analytical specification of Ph. Eur., BP, USP, E330, anhydrous, 99.5-100.5% (based on anhydrous substance)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)
Sigma-Aldrich
Pyridine, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)
Sigma-Aldrich
Dichloromethane, ACS reagent, ≥99.5%, contains 40-150 ppm amylene as stabilizer
Sigma-Aldrich
Acetic anhydride, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99% (GC)
Sigma-Aldrich
Pyridine, ReagentPlus®, ≥99%
Sigma-Aldrich
Pyridine, biotech. grade, ≥99.9%
Sigma-Aldrich
Iodine, flakes, ReagentPlus®, ≥99%
Sigma-Aldrich
N,N-Dimethylacetamide, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
Pyridine, ACS reagent, ≥99.0%
Sigma-Aldrich
Acetonitrile, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, ≥99.5% (GC)
Sigma-Aldrich
Iodine, puriss., meets analytical specification of Ph. Eur., BP, USP, 99.8-100.5%
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%