Trichloroacetaldehyde modified oligonucleotides

Bioorganic and Medicinal Chemistry Letters

Volumn 15, Issue 18, 2005, Pages 4118-4124

  Gaus, Hans ^a   Olsen, Phil ^a   Van Sooy, Kent ^a   Rentel, Claus ^a   Turney, Brett ^a   Walker, Kathleen L ^a   McArdle, James V ^a   Capaldi, Daniel C ^a  

^a ISIS PHARMACEUTICALS   (United States)

Author keywords

Antisense; Oligonucleotides; Trichloroacetaldehyde

Indexed keywords

CHLORAL; DICHLOROACETIC ACID; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE; OXYGEN; PHOSPHORUS;

ARTICLE; CHEMICAL STRUCTURE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LINKAGE ANALYSIS; MASS SPECTROMETRY; MOLECULAR MODEL; PHOSPHORUS NUCLEAR MAGNETIC RESONANCE; PROTON NUCLEAR MAGNETIC RESONANCE; SOLID; SYNTHESIS; ULTRAVIOLET RADIATION;

CHLORAL HYDRATE; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, ION EXCHANGE; DRUG CONTAMINATION; MASS SPECTROMETRY; MOLECULAR STRUCTURE; OLIGONUCLEOTIDES;

EID: 23644434394     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.06.018     Document Type: Article

References (33)

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14. Analytical SAX chromatography was performed using a Resource Q column (1 mL, Pharmacia). The column was held at 60°C and eluted over 40 min with a linear gradient of NaCl (1-2 M) in 0.1 M sodium phosphate (pH 11.5).
15. Preparative SAX chromatography was performed using a Q15HR column (50 × 100 mm, Waters). The sample was loaded onto the column in 0.1 M sodium phosphate (pH 11.5), then eluted with a gradient of NaCl in methanol and 0.1 M sodium phosphate (pH 11.5).
16. HPLC-UV-MS analysis of oligonucleotides was performed on an Agilent MSD1100 instrument. Separation was achieved using a C18 column held at 50°C and eluted with a gradient of acetonitrile in aqueous tripentylammonium acetate. The UV detector was set at 260 nm and mass spectra recorded from m/z = 1000 to 1700 in the negative ionization mode.
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19. 1 can give rise to the following dinucleoside phosphates with the stated frequencies: d(CpG), 2; d(CpC), 2; d(GpG), 2; d(TpC), 5; d(CpA), 2; d(GpC), 1; d(GpT), 1; d(ApT), 1; d(CpT), 2; d(ApG), 1. Of these ten, d(CpG) and d(GpC) are isobaric, as are d(TpC) and d(CpT).
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31. Trichloroacetal based protecting groups are resistant to acid hydrolysis and are normally cleaved by reduction (see Ref. 30).
32. Chloral levels ranged from none detected (limit of detection = 3 ppm) to 120 ppm.
33. Krotz, A., Capaldi, D., Gaus, H.-J.; Turney, B. Unpublished observations.