Synthesis of Fluorescence Turn-On DNA Hybridization Probe Using the DEA tC 2'-Deoxycytidine Analog

Curr Protoc Nucleic Acid Chem. 2018 Dec;75(1):e59. doi: 10.1002/cpnc.59. Epub 2018 Oct 18.

Abstract

DEA tC is a tricyclic 2'-deoxycytidine analog that can be incorporated into oligonucleotides by solid-phase synthesis and that exhibits a large fluorescence enhancement when correctly base-paired with a guanine base in a DNA-DNA duplex. The synthesis of DEA tC begins with 5-amino-2-methylbenzothiazole and provides the DEA tC nucleobase analog over five synthetic steps. This nucleobase analog is then silylated using N,O-bis(trimethylsilyl)acetamide and conjugated to Hoffer's chlorosugar to provide the protected DEA tC nucleoside in good yield. Following protective-group removal and chromatographic isolation of the β-anomer, dimethoxytritylation and phosphoramidite synthesis offer the monomer for solid-phase DNA synthesis. Solid-phase DNA synthesis conditions using extended coupling of the DEA tC amidite and a short deprotection time are employed to maximize efficiency. By following the protocols described in this unit, the DEA tC fluorescent probe can be synthesized and can be incorporated into any desired synthetic DNA oligonucleotide. © 2018 by John Wiley & Sons, Inc.

Keywords: 2′-deoxycytidine; fluorescence; guanine base; hybridization probe; nucleoside analog.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / chemistry
  • Carbon-13 Magnetic Resonance Spectroscopy
  • DNA / chemistry*
  • DNA Probes / chemical synthesis*
  • DNA Probes / chemistry
  • Deoxycytidine / chemistry*
  • Fluorescence
  • Fluorescent Dyes / chemical synthesis*
  • Fluorescent Dyes / chemistry
  • Nucleic Acid Conformation
  • Nucleic Acid Hybridization*
  • Phosphoric Acids / chemistry
  • Proton Magnetic Resonance Spectroscopy
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Amides
  • DNA Probes
  • Fluorescent Dyes
  • Phosphoric Acids
  • Deoxycytidine
  • DNA
  • phosphoramidic acid