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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, suitable for HPLC, gradient grade, ≥99.9%

Sigma-Aldrich

Pyridine, ReagentPlus^®, ≥99%

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%

Sigma-Aldrich

Acetonitrile, ACS reagent, ≥99.5%

Sigma-Aldrich

Acetonitrile, electronic grade, 99.999% trace metals basis

Sigma-Aldrich

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

Sigma-Aldrich

Dichloromethane, puriss. p.a., ACS reagent, reag. ISO, ≥99.9% (GC)

Supelco

Dichloromethane, analytical standard

Sigma-Aldrich

Dichloromethane, contains 40-150 ppm amylene as stabilizer, ACS reagent, ≥99.5%

Sigma-Aldrich

Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%

Sigma-Aldrich

Acetonitrile, HPLC Plus, ≥99.9%

Supelco

Dichloromethane, Selectophore^™, ≥99.5%

Sigma-Aldrich

Acetonitrile, biotech. grade, ≥99.93%

Supelco

Acetonitrile, analytical standard

Supelco

Methylene Chloride, Pharmaceutical Secondary Standard; Certified Reference Material

SAFC

N,N-Dimethylacetamide, Ph. Eur.

USP

Methyl alcohol, United States Pharmacopeia (USP) Reference Standard

Sigma-Aldrich

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

Sigma-Aldrich

Dichloromethane, biotech. grade, 99.9%, contains 40-150 ppm amylene as stabilizer

Supelco

Iodine, ReagentPlus^®, ≥99.8% (titration)

Sigma-Aldrich

Pyridine, biotech. grade, ≥99.9%

Sigma-Aldrich

Acetonitrile, for preparative HPLC, ≥99.8% (GC)

Sigma-Aldrich

Acetic anhydride, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99% (GC)

Sigma-Aldrich

Imidazole buffer Solution, BioUltra, 1 M in H₂O

Sigma-Aldrich

Iodine, ACS reagent, ≥99.8%, solid

Supelco

Pyridine, Pharmaceutical Secondary Standard; Certified Reference Material

Supelco

Pyridine, analytical standard

Sigma-Aldrich

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

Sigma-Aldrich

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

Supelco

N,N-Dimethylacetamide, analytical standard