A Carbazole-Derived Nitroxide That Is an Analogue of Cytidine: A Rigid Spin Label for DNA and RNA

J Org Chem. 2021 Sep 3;86(17):11647-11659. doi: 10.1021/acs.joc.1c01176. Epub 2021 Aug 19.

Abstract

A variety of semirigid and rigid spin labels comprise a valuable arsenal for measurements of biomolecular structures and dynamics by electron paramagnetic resonance (EPR) spectroscopy. Here, we report the synthesis and characterization of rigid spin labels Ċ and Ċm for DNA and RNA, respectively, that are carbazole-derived nitroxides and analogues of cytidine. Ċ and Ċm were converted to their phosphoramidites and used for their incorporation into oligonucleotides by solid-phase synthesis. Analysis of Ċ and Ċm by single-crystal X-ray crystallography verified their identity and showed little deviation from planarity of the nucleobase. Analysis of the continuous-wave (CW) EPR spectra of the spin-labeled DNA and RNA duplexes confirmed their incorporation into the nucleic acids and the line-shape was characteristic of rigid spin labels. Circular dichroism (CD) and thermal denaturation studies of the Ċ-labeled DNAs and Ċm-labeled RNAs indicated that the labels are nonperturbing of duplex structure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbazoles
  • Cytidine*
  • DNA
  • Electron Spin Resonance Spectroscopy
  • Nitrogen Oxides
  • RNA*
  • Spin Labels

Substances

  • Carbazoles
  • Nitrogen Oxides
  • Spin Labels
  • Cytidine
  • RNA
  • DNA
  • nitroxyl