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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

Imidazole, anhydrous, free-flowing, Redi-Dri^™, ACS reagent, ≥99%

Sigma-Aldrich

Imidazole, ReagentPlus^®, 99%, Redi-Dri^™, free-flowing

Sigma-Aldrich

Imidazole, for molecular biology, ≥99% (titration), free-flowing, Redi-Dri^™

Sigma-Aldrich

Methanol, ACS reagent, ≥99.8%

Sigma-Aldrich

Methanol, Absolute - Acetone free

Sigma-Aldrich

Water, suitable for HPLC

Sigma-Aldrich

Methanol, suitable for HPLC, ≥99.9%

Sigma-Aldrich

Water, HPLC Plus

Sigma-Aldrich

Acetonitrile solution, contains 10.0% acetone, 0.05% formic acid, 40.0% 2-propanol

Sigma-Aldrich

Methanol, suitable for HPLC

Supelco

Water, for TOC analysis

Sigma-Aldrich

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

Sigma-Aldrich

Triethylamine, SAJ first grade, ≥98.0%

Sigma-Aldrich

Methanol, JIS special grade, ≥99.8%

Sigma-Aldrich

Methanol, NMR reference standard

Sigma-Aldrich

Methanol, SAJ first grade, ≥99.5%

Sigma-Aldrich

Methanol, SAJ special grade

Supelco

Water, ACS reagent, for ultratrace analysis

Sigma-Aldrich

Benzyl azide solution, ~0.5 M in dichloromethane, ≥95.0% (HPLC)

Sigma-Aldrich

Imidazole, BioUltra, ≥99.5% (GC)

Sigma-Aldrich

Imidazole, puriss. p.a., ≥99.5% (GC)

Sigma-Aldrich

Methanol, anhydrous, 99.8%

Sigma-Aldrich

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

Sigma-Aldrich

Water, tested according to Ph. Eur.

Sigma-Aldrich

Triethylamine, BioUltra, ≥99.5% (GC)

Sigma-Aldrich

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

Sigma-Aldrich

Trichloroacetic acid, BioUltra, ≥99.5% (T)

Sigma-Aldrich

Imidazole, BioUltra, for molecular biology, ≥99.5% (GC)

Sigma-Aldrich

Azidomethyl phenyl sulfide, 95%

Sigma-Aldrich

Water, for molecular biology, sterile filtered