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

Abstract 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 bi...

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Autores principales:	Christopher P. Lawson, Anders F. Füchtbauer, Moa S. Wranne, Tristan Giraud, Thomas Floyd, Blaise Dumat, Nicolai K. Andersen, Afaf H. El-Sagheer, Tom Brown, Henrik Gradén, L. Marcus Wilhelmsson, Morten Grøtli
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Thymine Analogue Oligonucleotide Incorporation Fluorescent Base Analogues (FBAs) Natural Nucleobases MeCN Water Medicine R Science Q
Acceso en línea:	https://doaj.org/article/91467726e61f4f76abb1785ce4f6f727
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spelling	oai:doaj.org-article:91467726e61f4f76abb1785ce4f6f7272021-12-02T15:05:17ZSynthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue10.1038/s41598-018-31897-22045-2322https://doaj.org/article/91467726e61f4f76abb1785ce4f6f7272018-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-31897-2https://doaj.org/toc/2045-2322Abstract 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−1 in 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.Christopher P. LawsonAnders F. FüchtbauerMoa S. WranneTristan GiraudThomas FloydBlaise DumatNicolai K. AndersenAfaf H. El-SagheerTom BrownHenrik GradénL. Marcus WilhelmssonMorten GrøtliNature PortfolioarticleThymine AnalogueOligonucleotide IncorporationFluorescent Base Analogues (FBAs)Natural NucleobasesMeCN WaterMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Thymine Analogue Oligonucleotide Incorporation Fluorescent Base Analogues (FBAs) Natural Nucleobases MeCN Water Medicine R Science Q
spellingShingle	Thymine Analogue Oligonucleotide Incorporation Fluorescent Base Analogues (FBAs) Natural Nucleobases MeCN Water Medicine R Science Q Christopher P. Lawson Anders F. Füchtbauer Moa S. Wranne Tristan Giraud Thomas Floyd Blaise Dumat Nicolai K. Andersen Afaf H. El-Sagheer Tom Brown Henrik Gradén L. Marcus Wilhelmsson Morten Grøtli Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
description	Abstract 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−1 in 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.
format	article
author	Christopher P. Lawson Anders F. Füchtbauer Moa S. Wranne Tristan Giraud Thomas Floyd Blaise Dumat Nicolai K. Andersen Afaf H. El-Sagheer Tom Brown Henrik Gradén L. Marcus Wilhelmsson Morten Grøtli
author_facet	Christopher P. Lawson Anders F. Füchtbauer Moa S. Wranne Tristan Giraud Thomas Floyd Blaise Dumat Nicolai K. Andersen Afaf H. El-Sagheer Tom Brown Henrik Gradén L. Marcus Wilhelmsson Morten Grøtli
author_sort	Christopher P. Lawson
title	Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
title_short	Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
title_full	Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
title_fullStr	Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
title_full_unstemmed	Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue
title_sort	synthesis, oligonucleotide incorporation and fluorescence properties in dna of a bicyclic thymine analogue
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/91467726e61f4f76abb1785ce4f6f727
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Synthesis, oligonucleotide incorporation and fluorescence properties in DNA of a bicyclic thymine analogue

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