Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
Artikel i vetenskaplig tidskrift, 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.
Författare
Christopher Lawson
Göteborgs universitet
Anders Foller Füchtbauer
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Moa Sandberg Wranne
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Tristan Giraud
Chalmers, Kemi och kemiteknik, Kemiteknik
Tom Floyd
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Blaise Dumat
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Nicolai Krog Andersen
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Afaf H. El-Sagheer
University of Oxford
Suez University
T. Brown
University of Oxford
Henrik Gradén
AstraZeneca AB
Marcus Wilhelmsson
Chalmers, Kemi och kemiteknik, Kemi och biokemi
Morten Grötli
Göteborgs universitet
Scientific Reports
2045-2322 (ISSN) 20452322 (eISSN)
Vol. 8 1 13970Styrkeområden
Nanovetenskap och nanoteknik
Livsvetenskaper och teknik (2010-2018)
Ämneskategorier
Fysikalisk kemi
Annan medicinsk grundvetenskap
Organisk kemi
DOI
10.1038/s41598-018-31897-2