Synthesis and binding properties of oligo-2′-deoxyribonucleotides conjugated with triple-helix-specific intercalators: Benzo[e] and benzo[g] pyridoindoles

Serguei Vinogradov, Victoria Roig, Zinaida Sergueeva, Chi Hung Nguyen, Paola Arimondo, Nguyen T. Thuong, Emile Bisagni, Jian Sheng Sun, Claude Hélène, Ulysse Asseline

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

DNA binding compounds, such as benzo [e] (BePI) and benzo [g] pyridoindole (BgPI) derivatives, exhibit preferential stabilization of triple helices. We report here the synthesis of a series of pyrimidine triple-helix-forming oligo-2′-deoxyribonucleotides conjugated with these molecules. BePI was coupled to the 5-position of 2′-deoxyuridine via two linkers of different sizes attached to its 11-position and placed at either the 5′-end, inside the sequence, or at both the 5′-end and the internal positions using periodate oxidation of a diol-containing oligonucleotide followed by reductive coupling with amino-linked BePI. The same BePI derivatives were also linked to the oligonucleotide chain via internucleotidic phosphorothiolate or phosphoramidate linkages. A mixture of diastereoisomers was prepared as well as separate pure Rp and Sp isomers. A BePI derivative, with two different linkers attached to its 3-position, and BgPI derivatives were also linked to the 5-position of a 2′-deoxyuridine located at either the 5′-end or inside the sequence, as well as to the β-anomeric position of an additional 2′-deoxyribose placed inside the sequence. The binding properties of these oligonucleotide-benzopyridoindoles conjugates with their double-stranded DNA target was studied by absorption spectroscopy.

Original languageEnglish (US)
Pages (from-to)120-135
Number of pages16
JournalBioconjugate Chemistry
Volume14
Issue number1
DOIs
StatePublished - Jan 2003

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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    Vinogradov, S., Roig, V., Sergueeva, Z., Nguyen, C. H., Arimondo, P., Thuong, N. T., Bisagni, E., Sun, J. S., Hélène, C., & Asseline, U. (2003). Synthesis and binding properties of oligo-2′-deoxyribonucleotides conjugated with triple-helix-specific intercalators: Benzo[e] and benzo[g] pyridoindoles. Bioconjugate Chemistry, 14(1), 120-135. https://doi.org/10.1021/bc020038w