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Beilstein J Org Chem. 2018 Jan 10;14:114-129. doi: 10.3762/bjoc.14.7. eCollection 2018.

Fluorescent nucleobase analogues for base-base FRET in nucleic acids: synthesis, photophysics and applications.

Author information

1
Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
2
Department of Chemistry and Chemical Engineering, Chemistry and Biochemistry, Chalmers University of Technology, SE-412 96 Gothenburg, Sweden.
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Contributed equally

Abstract

Förster resonance energy transfer (FRET) between a donor nucleobase analogue and an acceptor nucleobase analogue, base-base FRET, works as a spectroscopic ruler and protractor. With their firm stacking and ability to replace the natural nucleic acid bases inside the base-stack, base analogue donor and acceptor molecules complement external fluorophores like the Cy-, Alexa- and ATTO-dyes and enable detailed investigations of structure and dynamics of nucleic acid containing systems. The first base-base FRET pair, tCO-tCnitro, has recently been complemented with among others the adenine analogue FRET pair, qAN1-qAnitro, increasing the flexibility of the methodology. Here we present the design, synthesis, photophysical characterization and use of such base analogues. They enable a higher control of the FRET orientation factor, κ2, have a different distance window of opportunity than external fluorophores, and, thus, have the potential to facilitate better structure resolution. Netropsin DNA binding and the B-to-Z-DNA transition are examples of structure investigations that recently have been performed using base-base FRET and that are described here. Base-base FRET has been around for less than a decade, only in 2017 expanded beyond one FRET pair, and represents a highly promising structure and dynamics methodology for the field of nucleic acids. Here we bring up its advantages as well as disadvantages and touch upon potential future applications.

KEYWORDS:

B-to-Z-DNA transition; FRET; Z-DNA; fluorescent base analogues; netropsin; nucleic acid structure and dynamics; quadracyclic adenines; tricyclic cytosines

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