Design and Biological Evaluation of Photo-Switchable Inhibitors

Melanie Füllbeck[1] (melanie.fuellbeck@charite.de)
Elke Michalsky[1] (elke.michalsky@charite.de)
Ines Stephanie Jaeger[1] (ines.jaeger@charite.de)
Peter Henklein[2] (peter.henklein@charite.de)
Hartmut Kuhn[2] (hartmut.kuehn@charite.de)
Karola Rück-Braun[3] (krueck@chem.tu-berlin.de)
Robert Preissner[1] (robert.preissner@charite.de)

[1]Berlin Center of Genome Based Bioinformatics, 3D Dataminig Group, Institute of Molecular Biology and Bioinformatics, University Medicine Berlin-Charité (CBF), Arnimallee 22, D-10117 Berlin, Germany
[2]Institute of Biochemistry, University Medicine Berlin-Charité, Monbijoustr. 2, D-10117 Berlin, Germany
[3]Institute of Chemistry, Technical University Berlin, Strasse des 17. Juni 135, D-10623 Berlin, Germany


Abstract

Photo-switchable compounds are becoming increasingly popular for a series of biological applications based on the reversible photo-control of structure and function of biomolecules. Three applications for the usage of BODTCM and hemithioindigo as photo-reactive compounds are described here. The structure of the villin headpiece was modified by replacing a part of the backbone with hemithioindigo, aiming at induction of the folding process by irradiation with a defined wavelength. The E-isomer of BODTCM was applied as potential inhibitor of the 12/15-lipoxygenase (12/15-LOX), which is implicated in the pathogenesis of inflammatory diseases. A required death domain for the binding of proapoptotic proteins (e.g. Bak) to the hydrophobic groove of antiapoptotic proteins is the BH3 helix. Inserting hemithioindigo into this short peptide, stabilization towards proteolytic degradation is achieved. Such photo-reactive compounds might be developed as potential drugs for a great variety of diseases.

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Japanese Society for Bioinformatics