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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

Methanol, analytical standard

Sigma-Aldrich

Imidazole, BioUltra, ≥99.5% (GC)

Sigma-Aldrich

Trichloroacetic acid, BioUltra, ≥99.5% (T)

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Trichloroacetic acid, ACS reagent, for the determination of Fe in blood according to Heilmeyer, ≥99.5%

Sigma-Aldrich

Azidomethyl phenyl sulfide, 95%

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2,6-Lutidine, ReagentPlus^®, 98%

Supelco

2,6-Lutidine, analytical standard

Sigma-Aldrich

2,6-Lutidine

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Methylamine solution, 40 wt. % in H₂O

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Imidazole, ReagentPlus^®, 99%

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Water, tested according to Ph. Eur.

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Triethylamine, puriss. p.a., ≥99.5% (GC)

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Triethylamine, ampule, ≥99.5% (GC)

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Triethylamine, ≥99.5%

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Water, Molecular Biology, sterile filtered

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Water, for cell biology, sterile ultrafiltered

Supelco

Water, suitable for HPCE, suitable for luminescence, suitable for UV/Vis spectroscopy

Sigma-Aldrich

Triethylamine, BioUltra, ≥99.5% (GC)

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Imidazole, ≥99% (titration), crystalline

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Imidazole, ACS reagent, ≥99% (titration)

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Imidazole, Molecular Biology, ≥99% (titration)

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Trichloroacetic acid, ACS reagent, ≥99.0%

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Trichloroacetic acid, ≥99.0% (titration)

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Trichloroacetic acid, BioXtra, ≥99.0%

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E-Toxate^™ Water, endotoxin, free

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Imidazole, puriss. p.a., ≥99.5% (GC)

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Trichloroacetic acid, suitable for electrophoresis, suitable for fixing solution (for IEF and PAGE gels), ≥99%

Sigma-Aldrich

Water, PCR Reagent

Sigma-Aldrich

Triethylamine, for amino acid analysis, ≥99.5% (GC)

Sigma-Aldrich

Methylamine solution, 33 wt. % in absolute ethanol ((denatured with 1% toluene))