Søren Preus

Aarhus University

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

L. Marcus Wilhelmsson

Chalmers University of Technology

Victoria Birkedal

Aarhus University

Lasse L. Hildebrandt

Aarhus University

Bo Albinsson

Chalmers University of Technology

Kristine Kilså

University of Copenhagen

Karl Börjesson

University of Gothenburg

Tom Brown

ATDBio (United Kingdom)

Sofie L. Noer

Aarhus University

Daniel Gudnason

Aarhus University

Morten Grøtli

University of Gothenburg

Cooperative Institutions

Chalmers University of Technology

Aarhus University

University of Gothenburg

University of Southampton

Centre National de la Recherche Scientifique

University of Copenhagen

Suez University

Suez Canal University

Danish National Research Foundation

Technical University of Denmark

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Quadracyclic Adenine: A Non‐Perturbing Fluorescent Adenine Analogue

Chemistry - A European Journal (2012)

Anke Dierckx François‐Alexandre Miannay Nouha Ben Gaied Søren Preus Markus L. Björck

Abstract Fluorescent‐base analogues (FBAs) comprise a group of increasingly important molecules for the investigation of nucleic acid structure and dynamics as well as of interactions between nucleic acids and other molecules. Here, we report on the synthesis, detailed spectroscopic characterisation and base‐pairing properties of a new environment‐sensitive fluorescent adenine analogue, quadracyclic adenine (qA). After developing an efficient route of synthesis for the phosphoramidite of qA it was incorporated into DNA in high yield by using standard solid‐phase synthesis procedures. In DNA qA serves as an adenine analogue that preserves the B‐form and, in contrast to most currently available FBAs, maintains or even increases the stability of the duplex. We demonstrate that, unlike fluorescent adenine analogues, such as the most commonly used one, 2‐aminopurine, and the recently developed triazole adenine, qA shows highly specific base‐pairing with thymine. Moreover, qA has an absorption band outside the absorption of the natural nucleobases (>300 nm) and can thus be selectively excited. Upon excitation the qA monomer displays a fluorescence quantum yield of 6.8 % with an emission maximum at 456 nm. More importantly, upon incorporation into DNA the fluorescence of qA is significantly less quenched than most FBAs. This results in quantum yields that in some sequences reach values that are up to fourfold higher than maximum values reported for 2‐aminopurine. To facilitate future utilisation of qA in biochemical and biophysical studies we investigated its fluorescence properties in greater detail and resolved its absorption band outside the DNA absorption region into distinct transition dipole moments. In conclusion, the unique combination of properties of qA make it a promising alternative to current fluorescent adenine analogues for future detailed studies of nucleic acid‐containing systems.

Nucleobase

Quantum yield

Phosphoramidite

Thymine

10.1002/chem.201103419

Cite

Citations (35)

Photophysical and structural properties of the fluorescent nucleobase analogues of the tricyclic cytosine (tC) family

Physical Chemistry Chemical Physics (2010)

Søren Preus Kristine Kilså L. Marcus Wilhelmsson Bo Albinsson

Fundamental insight into the unique fluorescence and nucleobase-mimicking properties of the fluorescent nucleobase analogues of the tC family is not only vital in explaining the behaviour of these probes in nucleic acid environments, but will also be profitable in the development of new and improved fluorescent base analogues. Here, temperature-dependent fluorescence quantum yield measurements are used to successfully separate and quantify the temperature-dependent and temperature-independent non-radiative excited-state decay processes of the three nucleobase analogues tC, tCO and tCnitro; all of which are derivatives of a phenothiazine or phenoxazine tricyclic framework. These results strongly suggest that the non-radiative decay process dominating the fast deactivation of tCnitro is an internal conversion of a different origin than the decay pathways of tC and tCO. tCnitro is reported to be fluorescent only in less dipolar solvents at room temperature, which is explained by an increase in excited-state dipole moment along the main non-radiative decay pathway, a suggestion that applies in the photophysical discussion of large polycyclic nitroaromatics in general. New insight into the ground and excited-state potential energy surfaces of the isolated tC bases is obtained by means of high level DFT and TDDFT calculations. The S0 potential energy surfaces of tC and tCnitro possess two global minima corresponding to geometries folded along the middle sulfur–nitrogen axis separated by an energy barrier of 0.05 eV as calculated at the B3LYP/6-311+G(2d,p) level. The ground-state potential energy surface of tCO is also predicted to be shallow along the bending coordinate but with an equilibrium geometry corresponding to the planar conformation of the tricyclic framework, which may explain some of the dissimilar properties of tC and tCO in various confined (biological) environments. The S1 equilibrium geometries of all three base analogues are predicted to be planar. These results are discussed in the context of the tC bases positioned in double-stranded DNA scenarios.

Nucleobase

Quantum yield

10.1039/c000625d

Cite

Citations (40)

Excitation energy transfer in novel acetylenic perylene diimide scaffolds

New Journal of Chemistry (2008)

David R. Shanks Søren Preus Katrine Qvortrup Tue Hassenkam Mogens Brøndsted Nielsen

New perylene diimide (PDI) dimers (bis(PDI)s) with either tetraethynylethene (TEE) or 2,4-hexadiyne as the bridging unit were synthesized and the degree of intramolecular communication between the two PDI units was investigated as a function of the spacer unit and solvent polarity by absorption and emission spectroscopies, electrochemistry, and by atomic force microscopy (AFM). The experiments reveal that energy transfer occurs between TEE and PDI, and between PDI units. In the bis(PDI)-TEE system, flexible linkers allowed for intramolecular π–π stacking of the PDI chromophores in solution. The degree of stacking is solvent dependent, being more pronounced in non-polar solvents. The molecules were also found to self-assemble at a mica surface by intermolecular π–π interactions and to form fibrilar structures. Intermolecular excitation energy transfer was observed at the surface.

Diimide

Chromophore

10.1039/b811565f

Cite

Citations (14)

Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design

Scientific Reports (2015)

Anders Foller Larsen Blaise Dumat Moa S. Wranne Christopher P. Lawson Søren Preus

Abstract Fluorescent base analogues (FBAs) comprise a family of increasingly important molecules for the investigation of nucleic acid structure and dynamics. We recently reported the quantum chemical calculation supported development of four microenvironment sensitive analogues of the quadracyclic adenine (qA) scaffold, the qANs, with highly promising absorptive and fluorescence properties that were very well predicted by TDDFT calculations. Herein, we report on the efficient synthesis, experimental and theoretical characterization of nine novel quadracyclic adenine derivatives. The brightest derivative, 2-CNqA, displays a 13-fold increased brightness (εΦ F = 4500) compared with the parent compound qA and has the additional benefit of being a virtually microenvironment-insensitive fluorophore, making it a suitable candidate for nucleic acid incorporation and use in quantitative FRET and anisotropy experiments. TDDFT calculations, conducted on the nine novel qAs a posteriori , successfully describe the relative fluorescence quantum yield and brightness of all qA derivatives. This observation suggests that the TDDFT-based rational design strategy may be employed for the development of bright fluorophores built up from a common scaffold to reduce the otherwise costly and time-consuming screening process usually required to obtain useful and bright FBAs.

Rational design

10.1038/srep12653

Cite

Citations (18)

A DNA based five-state switch with programmed reversibility

Chemical Communications (2012)

Jonathan R. Burns Søren Preus Daniel Singleton Eugen Stulz

A programmable switch based on a DNA hairpin loop is functionalised with a rigid or flexible porphyrin or FAM and TAMRA FRET pair, which provides insight into the restructuring of the hairpin as well as porphyrin–porphyrin coupling. The switch contains five discrete states which can be accessed independently and followed by real-time spectroscopy, opening the way to a quinary computing code.

Quinary

10.1039/c2cc35799b

Cite

Citations (11)

Function and Movement of a DNA Actuator Investigated by Single Molecule Fret Microscopy

Biophysical Journal (2014)

Lasse L. Hildebrandt Zhao Zhang Søren Preus Kurt V. Gothelf Victoria Birkedal

Single-molecule FRET

A-DNA

Piston (optics)

Molecular machine

10.1016/j.bpj.2013.11.1321

Cite

Citations (0)

Folding dynamics and conformational heterogeneity of human telomeric G-quadruplex structures in Na⁺solutions by single molecule FRET microscopy

Nucleic Acids Research (2015)

Sofie L. Noer Søren Preus Daniel Gudnason Mikayel Aznauryan Jean‐Louis Mergny

G-quadruplex structures can occur throughout the genome, including at telomeres. They are involved in cellular regulation and are potential drug targets. Human telomeric G-quadruplex structures can fold into a number of different conformations and show large conformational diversity. To elucidate the different G-quadruplex conformations and their dynamics, we investigated telomeric G-quadruplex folding using single molecule FRET microscopy in conditions where it was previously believed to yield low structural heterogeneity. We observed four FRET states in Na+ buffers: an unfolded state and three G-quadruplex related states that can interconvert between each other. Several of these states were almost equally populated at low to medium salt concentrations. These observations appear surprising as previous studies reported primarily one G-quadruplex conformation in Na+ buffers. Our results permit, through the analysis of the dynamics of the different observed states, the identification of a more stable G-quadruplex conformation and two transient G-quadruplex states. Importantly these results offer a unique view into G-quadruplex topological heterogeneity and conformational dynamics.

G-quadruplex

Single-molecule FRET

Folding (DSP implementation)

10.1093/nar/gkv1320

Cite

Citations (69)

Multifluorophore DNA Origami Beacon as a Biosensing Platform

ACS Nano (2018)

Denis Selnihhin Steffen M. Sparvath Søren Preus Victoria Birkedal Ebbe Sloth Andersen

Biosensors play increasingly important roles in many fields, from clinical diagnosis to environmental monitoring, and there is a growing need for cheap and simple analytical devices. DNA nanotechnology provides methods for the creation of sophisticated biosensors, however many of the developed DNA-based sensors are limited by cumbersome and time-consuming readouts involving advanced experimental techniques. Here we describe design, construction, and characterization of an optical DNA origami nanobiosensor device exploiting arrays of precisely positioned organic fluorophores. Two arrays of donor and acceptor fluorophores make up a multifluorophore Förster resonance energy-transfer pair that results in a high-output signal for microscopic detection of single devices. Arrangement of fluorophores into arrays increases the signal-to-noise ratio, allowing detection of signal output from singular biosensors using a conventional fluorescence microscopy setup. Single device analysis enables detection of target DNA sequences in concentrations down to 100 pM in <45 min. We expect that the presented nanobiosensor can function as a general platform for incorporating sensor modules for a variety of targets and that the strong signal amplification properties may allow detection in portable microscope systems to be used for biosensor applications in the field.

SIGNAL (programming language)

10.1021/acsnano.8b01510

Cite

Citations (110)

Characterization of Nucleobase Analogue FRET Acceptor tC_nitro

The Journal of Physical Chemistry B (2009)

Søren Preus Karl Börjesson Kristine Kilså Bo Albinsson L. Marcus Wilhelmsson

The fluorescent nucleobase analogues of the tricyclic cytosine (tC) family, tC and tCO, possess high fluorescence quantum yields and single fluorescence lifetimes, even after incorporation into double-stranded DNA, which make these base analogues particularly useful as fluorescence resonance energy transfer (FRET) probes. Recently, we reported the first all-nucleobase FRET pair consisting of tCO as the donor and the novel tCnitro as the acceptor. The rigid and well-defined position of this FRET pair inside the DNA double helix, and consequently excellent control of the orientation factor in the FRET efficiency, are very promising features for future studies of nucleic acid structures. Here, we provide the necessary spectroscopic and photophysical characterization of tCnitro needed in order to utilize this probe as a FRET acceptor in nucleic acids. The lowest energy absorption band from 375 to 525 nm is shown to be the result of a single in-plane polarized electronic transition oriented ∼27° from the molecular long axis. This band overlaps the emission bands of both tC and tCO, and the Förster characteristics of these donor−acceptor pairs are calculated for double-stranded DNA scenarios. In addition, the UV−vis absorption of tCnitro is monitored in a broad pH range and the neutral form is found to be totally predominant under physiological conditions with a pKa of 11.1. The structure and electronic spectrum of tCnitro is further characterized by density functional theory calculations.

Nucleobase

Acceptor

10.1021/jp909471b

Cite

Citations (41)

Fast and User-Friendly Single-Molecule FRET Microscopy Software

Biophysical Journal (2015)

Søren Preus Lasse L. Hildebrandt Sofie L. Noer Victoria Birkedal

Single-molecule FRET

Biomolecule

10.1016/j.bpj.2014.11.898

Cite

Citations (1)