Molecular Imaging Probes

Molecular imaging probes are agents used to visualize, characterize and quantify biological processes in living systems.

Fluorescent nucleic acid base analogs (FBAs) are structural analogs of the standard DNA/RNA bases, which are highly fluorescent, and form Watson-Crick hydrogen bonds with complementary bases. We are developing FBAs for studying structure and dynamics of nucleic acids.

Collaborators include: Wilhelmsson and Lemurell.

Synthesis, oligonucleotide incorporation and fluorescence properties of a bicyclic thymine analogue in DNA, Christopher P. Lawson, Anders F. Füchtbauer, Moa S. Wranne, Tristan Giraud, Thomas Floyd, Blaise Dumat, Nicolai Krog Andersen, Afaf El-Sagheer, Tom Brown, Henrik Gradén, Marcus Wilhelmsson, Morten Grøtli. Sci. Rep. 2018, 8, 13970; doi: 10.1038/s41598-018-31897-2

Pentacyclic adenine: a versatile and exceptionally bright fluorescent DNA base analog, Mattias Bood, Anders F. Füchtbauer, Moa S. Wranne, Jong Jin Ro, Sangamesh Sarangamath, Afaf H. El-Sagheer, Déborah L. M. Rupert, Rachel Fisher, Steven W. Magennis, Anita C. Jones, Fredrik Höök, Tom Brown, Byeang Hyean Kim, Anders Dahlén, L. Marcus Wilhelmsson and Morten Grøtli. Chem. Sci., 2018, 9, 3494 – 3502.

Multiphoton microscopy is a benchmark tool in biomedical research, used for the fluorescence imaging in cellular environments. This has important implications for disease diagnosis and the monitoring of therapy response.

In conventional two-photon microscopy the fluorescence intensity of the employed molecular probe is proportional to the square of the excitation light intensity, implying that the fluorescence from the sample is confined around the focal point, yielding good spatial resolution. The spatial resolution can be dramatically improved by drawing on higher-order processes such as four photon absorption.

As a part of an EU funded project entitled Breaking the Resolution Limit in Two-Photon Microscopy Using Negative Photochromism (4for2), we are developing molecules that combine two mechanistically entangled two-photon processes for the generation of a fluorescence output. This is possible by merging two-photon absorption, two-photon FRET-induced photoisomerization, and negative photochromism.

Collaborators include Andréasson, Pischel and Hofkens.