title: Design and biological evaluation of photo-switchable inhibitors.
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.
authors.affiliation: 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. melanie.fuellbeck@charite.de
authors.forename: Melanie
authors.initials: M
authors.lastname: Füllbeck
authors.forename: Elke
authors.initials: E
authors.lastname: Michalsky
authors.forename: Ines Stephanie
authors.initials: IS
authors.lastname: Jaeger
authors.forename: Peter
authors.initials: P
authors.lastname: Henklein
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuhn
authors.forename: Karola
authors.initials: K
authors.lastname: Rück-Braun
authors.forename: Robert
authors.initials: R
authors.lastname: Preissner
mesh_terms: D001393:Azoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors; D006801:Humans; D007202:Indicators and Reagents / Q000138:chemical synthesis / Q000494:pharmacology; D007203:Indigo Carmine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D054833:Isoindoles; D019169:Jurkat Cells; D008027:Light; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D008840:Microfilament Proteins / Q000737:chemistry / Q000494:pharmacology; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D013379:Substrate Specificity
chemical_list: D001393:Azoles; D051023:BH3 Interacting Domain Death Agonist Protein; C474007:Bax protein (53-86); D007202:Indicators and Reagents; D054833:Isoindoles; D016859:Lipoxygenase Inhibitors; D008840:Microfilament Proteins; D016566:Organoselenium Compounds; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C026615:villin; C042986:ebselen; C009466:thioindigo; D007203:Indigo Carmine