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

Anna Lena Johanna Segler, Snorri Th Sigurdsson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)11647-11659
Number of pages13
JournalJournal of Organic Chemistry
Volume86
Issue number17
DOIs
Publication statusPublished - 3 Sept 2021

Bibliographical note

Funding Information: We acknowledge financial support from the Icelandic Research Fund (206708). We thank Dr. S. Jonsdottir and Dr. T. Halbritter for assistance with collecting analytical data for structural characterization of new compounds, Prof. K. K. Damodaran for solving the crystal structures of Ċ and Ċm , and members of the Sigurdsson research group for helpful discussions. Publisher Copyright: © 2021 American Chemical Society.

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