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
Moa Sandberg Wranne
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Tristan Giraud
Chalmers, Chemistry and Chemical Engineering, Chemical Technology
Tom Floyd
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Blaise Dumat
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Nicolai Krog Andersen
Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry
Afaf H. El-Sagheer
University of Oxford
Suez University
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) 20452322 (eISSN)
Vol. 8 1 13970Areas of Advance
Nanoscience and Nanotechnology
Life Science Engineering (2010-2018)
Subject Categories
Physical Chemistry
Other Basic Medicine
Organic Chemistry
DOI
10.1038/s41598-018-31897-2