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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

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

Sigma-Aldrich

Pyridine, ACS reagent, ≥99.0%

Sigma-Aldrich

Pyridine, ReagentPlus^®, ≥99%

Sigma-Aldrich

Acetic anhydride

SAFC

N,N-Dimethylacetamide, Ph. Eur.

Sigma-Aldrich

Pyridine, suitable for HPLC, ≥99.9%

Sigma-Aldrich

Acetonitrile, suitable for HPLC-GC, ≥99.8% (GC)

USP

Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard

Sigma-Aldrich

Iodine, ReagentPlus^®, 99.7% trace metals basis, beads, 1-3 mm

Sigma-Aldrich

Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)

Sigma-Aldrich

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

Sigma-Aldrich

Iodine, flakes, ReagentPlus^®, ≥99%

Sigma-Aldrich

Pyridine, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥99.5% (GC)

Sigma-Aldrich

Pyridine, ReagentPlus^®, ≥99%

Sigma-Aldrich

Dichloromethane, puriss., meets analytical specification of Ph. Eur., NF, ≥99% (GC)

Sigma-Aldrich

N,N-Dimethylacetamide, puriss. p.a., ≥99.5% (GC)

Sigma-Aldrich

Iodine, puriss., ≥99.5% (RT), particles (round)

Supelco

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

Sigma-Aldrich

Acetonitrile, for chromatography

Sigma-Aldrich

Acetic anhydride, JIS special grade

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ special grade

Sigma-Aldrich

Acetic anhydride, SAJ first grade, ≥93.0%

Sigma-Aldrich

Pyridine, JIS special grade, ≥99.5%

Sigma-Aldrich

Citric acid, SAJ first grade, ≥99.5%

Sigma-Aldrich

Dichloromethane, SAJ first grade, ≥99.0%

Sigma-Aldrich

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

Sigma-Aldrich

Acetonitrile, JIS special grade, ≥99.5%

Sigma-Aldrich

Acetonitrile, SAJ first grade, ≥99.0%

Sigma-Aldrich

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

Sigma-Aldrich

N,N-Dimethylacetamide, SAJ first grade, ≥99.0%