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, Fysikalisk kemi

Moa Sandberg Wranne

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Tristan Giraud

Chalmers, Kemi och kemiteknik, Kemiteknik

Tom Floyd

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Blaise Dumat

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Nicolai Krog Andersen

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Afaf H. El-Sagheer

Suez University

University of Oxford

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)

Vol. 8 1 13970

Ämneskategorier

Fysikalisk kemi

Annan medicinsk grundvetenskap

Organisk kemi

DOI

10.1038/s41598-018-31897-2

Mer information

Senast uppdaterat

2018-12-10