The prooligonucleotide approach IV: Synthesis of chimeric prooligonucleotides with 6 enzymolabile masking groups and unexpected desulfurization side reaction

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 3, 1997, Pages 263-268

  Tosquellas, Guilhem ^a   Morvan, François ^a   Rayner, Bernard ^a   Imbach, Jean Louis ^a  

^a UNIVERSITÉ DE MONTPELLIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; PRODRUG;

ARTICLE; CELL LYSATE; CONTROLLED STUDY; DRUG PURIFICATION; DRUG SYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HYDROLYSIS; IN VITRO STUDY; MASS SPECTROMETRY; METHODOLOGY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS;

EID: 0031552079     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00616-6     Document Type: Article

References (16)

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10. 10. Oligo 3 was synthesized starting with an alpha-thymidine with a 3′-3′ internucleosidic linkage, in order to protect the oligo against 3′-exonucleases present in TCE. Debart, F.; Tosquellas, G., Rayner, B.; Imbach, J. L. Bioorg. Med. Chem. Lett. 1994, 4, 1041.
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14. 14 Alkylation of 5 was monitored by HPLC. MS coupling with negative electrospray mode (m/z) : 4 [M-H]-: 1118, 5 [M-H]-: 889, 6a-b [M-H]-:1004, 7a-b [M-H]-: 874, 8a-b [M-H]-: 988.
15. 15. Several controls were done in order to determine the nature of this desulfurization, including addition of EDTA 0.1M to trap possible metal ions or using silanized flasks to avoid any interaction with Si-OH function of glass or addition of sodium iodide to try to increase the amount of desulfurization. All these conditions did not bring any variation. Finally alkylation with other kind of alkylating agents e. g. bromo-phenyl or 4-(iodoacetamido)fluorescein led to fully alkylated oligos without any desulfurization.
16. 16. Perigaud, C.; Aubertin, A.-M.; Benzaria, S.; Pelicano, H.; Girardet, J.-L.; Maury, G.; Gosselin, G.; Kirn, A.; Imbach, J.-L. Biochem. Pharmacol. 1994, 48, 11.