Synthesis and redox-active base-pairing properties of DNA incorporating mercapto C-nucleosides

Akihiko Hatano, Seiji Makita, Masayuki Kirihara

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Here, we describe the synthesis and incorporation of the nucleoside base analogue C-deoxyribonucleoside 3 carrying thiophenol into DNA. The 1′-β compound 3 was synthesized by Friedel-Crafts alkylation, followed by deprotection. The coupling reaction with 3,5-ditoluoyl-1-α/ β-methoxy-2-deoxy-d-ribose and diphenyldisulfide in the presence of SnCl4 afforded the α/β mixture 2 (β/α=2.8), and the β-form was separated by silica gel chromatography. After formation of the phosphoramidite derivative, the C-nucleoside 3 was incorporated into DNA. When the mercapto-bases were incorporated into complementary singled-stranded (ss) DNAs, the resulting duplex displayed high thermal stabilization on treatment with bubbling O2 (Tm 73°C), but was destabilized in the presence of mercaptoethanol (Tm 33°C). CD spectra showed that the duplex had a right-handed double-stranded structure. Imino proton NMR studies of temperature stability suggested that the strength of hydrogen bonding around the mercapto C-nucleoside was larger when treated with bubbling O2 than when in treated with reducing agent. Thus, formation of the base-to-base disulfide bond increased the stability of the duplex; correspondingly, reduction of the disulfide to two thiol bases destabilized the DNA reversibly. The duplex-forming disulfide base pair showed resistance to exonulease III. The present strategy could be used to introduce new functionalities into cells and novel biomaterials.

Original languageEnglish
Pages (from-to)1723-1730
Number of pages8
JournalTetrahedron
Volume61
Issue number7
DOIs
Publication statusPublished - 2005 Feb 14
Externally publishedYes

Fingerprint

Nucleosides
Disulfides
DNA
Deoxyribonucleosides
Ribose
Mercaptoethanol
Silica Gel
Reducing Agents
Alkylation
Biocompatible Materials
Chromatography
Sulfhydryl Compounds
Protons
Hydrogen bonds
Stabilization
Nuclear magnetic resonance
Derivatives
Oxidation-Reduction
Temperature

Keywords

  • Disulfide base pairing
  • DNA

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

Synthesis and redox-active base-pairing properties of DNA incorporating mercapto C-nucleosides. / Hatano, Akihiko; Makita, Seiji; Kirihara, Masayuki.

In: Tetrahedron, Vol. 61, No. 7, 14.02.2005, p. 1723-1730.

Research output: Contribution to journalArticle

Hatano, Akihiko ; Makita, Seiji ; Kirihara, Masayuki. / Synthesis and redox-active base-pairing properties of DNA incorporating mercapto C-nucleosides. In: Tetrahedron. 2005 ; Vol. 61, No. 7. pp. 1723-1730.
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