Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
Journal article, 2018

Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M−1cm−1in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.

Author

Christopher Lawson

University of Gothenburg

Anders Foller Füchtbauer

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Moa Sandberg Wranne

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Tristan Giraud

Chalmers, Chemistry and Chemical Engineering, Chemical Technology

Tom Floyd

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Blaise Dumat

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Nicolai Krog Andersen

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Afaf H. El-Sagheer

Suez University

University of Oxford

T. Brown

University of Oxford

Henrik Gradén

AstraZeneca AB

Marcus Wilhelmsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry

Morten Grötli

University of Gothenburg

Scientific Reports

2045-2322 (ISSN)

Vol. 8 1 13970

Subject Categories

Physical Chemistry

Other Basic Medicine

Organic Chemistry

DOI

10.1038/s41598-018-31897-2

More information

Latest update

12/10/2018