Fakultät für Chemie und Pharmazie
Refine
Has Fulltext
- yes (44)
Is part of the Bibliography
- yes (44)
Year of publication
Document Type
- Doctoral Thesis (37)
- Journal article (4)
- Master Thesis (2)
- Preprint (1)
Keywords
- Elektrochemie (3)
- Polymere (3)
- Elektronentransfer (2)
- Femtosekundenspektroskopie (2)
- Lithium-Ionen-Akkumulator (2)
- Nanopartikel (2)
- Polyoxazoline (2)
- Tissue Engineering (2)
- Additive Fertigung (1)
- Adenomatous-polyposis-coli-Protein (1)
- Adipose Tissue (1)
- Adverse outcome pathway (AOP) (1)
- Ag-DNA (1)
- Akzeptorgruppe (1)
- Aluminium-copper (1)
- Alzheimerkrankheit (1)
- Anode (1)
- Anorganische Chemie (1)
- Arzneimitteldesign (1)
- Aspergillose (1)
- Aspergillosis (1)
- Atemwege (1)
- Aushärtung (1)
- Bakteriorhodopsin (1)
- Batterie (1)
- Beschichtung (1)
- Biofabrication of hydrogels (1)
- Bioinks (1)
- Biolayerinterferometrie (1)
- Biomaterial (1)
- Biotransformation (1)
- Blei (1)
- Bleiakkumulator (1)
- Bor (1)
- Borheterocyclen (1)
- Borole (1)
- Boryl Anion (1)
- CE Proteaes (1)
- CTGF (1)
- CYR61 (1)
- Calciumhydroxid (1)
- Carbon additives (1)
- Carbon surface chemistry (1)
- Cascades (1)
- Chemical modification of biopolymers (1)
- Chemische Synthese (1)
- Chiral-sensitive Specktroskopie (1)
- Chiralität <Chemie> (1)
- Chlamydia trachomatis (1)
- Chondrogenic differentiation (1)
- Chromophor (1)
- Colloidal Stability (1)
- Colonkrebs (1)
- Connective Tissue Growth Factor (1)
- Cystein (1)
- Cytochrom-P450-Enzyme, Carboxylesterasen, Glutathion-S-Transferasen (1)
- DNA-encapsulated silver nanoclusters (1)
- DUB (1)
- Dectin-1 (1)
- Degradation (1)
- Dendrimere (1)
- Dendrimers (1)
- Deuteriumaustausch (1)
- Diamant (1)
- Diboren (1)
- Digitale Signalverarbeitung (1)
- Donorgruppe (1)
- Dynamic charge acceptance (1)
- Einseitige Kernspinresonanz (1)
- Elastizität (1)
- Electron Transfer (1)
- Elektrochromie (1)
- Elektron-Transfer (1)
- Endothelzelle (1)
- Energie-Transfer (1)
- Energy Transfer (1)
- Farbstoff (1)
- Fettgewebe (1)
- Fibrin (1)
- Fluorescence Upconversion (1)
- Fluoreszenz Aufkonversion (1)
- Foldamer (1)
- Foldamere (1)
- Foldamers (1)
- Fragmentscreening (1)
- Functional hydrophilic polymers (1)
- Gerichtete Erstarrung (1)
- Gold-Nanoparticles (1)
- HDAC (1)
- HPLC/UV, HPLC/fluorescence, LC/MS/MS analysis (1)
- HPLC/UV-, HPLC/Fluoreszenz-, LC/MS/MS-Analyse (1)
- Halobacterium halobium (1)
- Heteroaromaten (1)
- Higher-coordinate Compounds (1)
- Histon-Deacetylase (1)
- Hybridpolymere (1)
- Hydrogel (1)
- Hydrogels (1)
- Hypervalentes Molekül (1)
- Höherkoordinierte Verbdinungen (1)
- Impedanzspektroskopie (1)
- Implantat (1)
- In vitro (1)
- In vitro rat (1)
- In vitro testing (1)
- In-vitro-Assays (1)
- Inhalation (1)
- Inhibition (1)
- Inhibitor (1)
- Interleukin (1)
- Iron Oxide Nanoparticles (1)
- Kaskaden (1)
- Kathode (1)
- Klebstoff (1)
- Knochen (1)
- Knochenersatz (1)
- Knorpel (1)
- Kofaktorbindung (1)
- Kohlenstoff (1)
- Komposit (1)
- Konjugate (1)
- Konjugierte Polymere (1)
- Laserspektroskopie (1)
- Lead-acid batteries (1)
- Lithium-Ionen-Batterie (1)
- Lithium-ion Battery (1)
- Magnetische Kernresonanz (1)
- Maschinelles Lernen (1)
- Mesenchymzelle (1)
- Messenger-RNP (1)
- Messenger-RNS (1)
- Modifikation (1)
- Monoschicht (1)
- Multifunctionalisability (1)
- Myc (1)
- Nanodiamant (1)
- Nanodraht (1)
- Nanogels (1)
- Nanoröhre (1)
- Nanostrukturiertes Material (1)
- Nanotubular coatings (1)
- Nanotubuläre Beschichtungen (1)
- Native Chemical Ligation (1)
- Nephrotoxicity (1)
- Organische Sulfide (1)
- Oxidativer Stress (1)
- Oxygen diffusion hardening (1)
- Oxytosis (1)
- PCL (1)
- PE-X (1)
- PLGA (1)
- PVD Beschichtung (1)
- PVD coatings (1)
- PVD-Verfahren (1)
- Pentakoordination (1)
- Pflanzenextrakte (1)
- Photoswitch (1)
- Polarimetrie (1)
- Poly(2-oxazoline)s (1)
- Poly(glycidol)s (1)
- Polycaprolacton (1)
- Polyglycidol (1)
- Polylactid-co-Glycolid (1)
- Polymer (1)
- Polymer Science (1)
- Polymer-peptide-conjugate (1)
- Polymers (1)
- Polyoxazolines (1)
- Protein-Protein-Interaktion (1)
- Protein-Protein-Wechselwirkung (1)
- Protonenpumpe (1)
- Purpurmembran (1)
- QIVIVE (1)
- RNA binding proteins (1)
- Rapid Prototyping <Fertigung> (1)
- Ratte (1)
- Rekonstitution (1)
- Risk Assessment (1)
- SMN complex (1)
- SMN-Komplex (1)
- Sauerstoffdiffusionshärtung (1)
- Silicium (1)
- Silicium(II)-Komplexe (1)
- Silicium(IV)-Komplexe (1)
- Siliciumkomplexe (1)
- Silicon(II) Complexes (1)
- Silicon(IV) Complexes (1)
- Silylen (1)
- Small nuclear RNP (1)
- Spleißosom (1)
- Squaraine (1)
- Squaraines (1)
- State Estimation (1)
- Sternpolymere (1)
- Stoffwechsel (1)
- Support Vector Regression (1)
- Tantal (1)
- Therapeutisches System (1)
- Thioether-Poly(glycidol) (1)
- Thiol-Ene-Click-Chemie (1)
- Ti(Ag) Beschichtungen (1)
- Ti(Ag) coatings (1)
- Transient Absorption (1)
- Transiente Absorption (1)
- Triarylamine (1)
- Tritiumaustausch (1)
- UV-VIS-Spektroskopie (1)
- Ubiquitin (1)
- Ultrakurzzeitspektroskopie (1)
- Ultraschall (1)
- Ultraschallprüfung (1)
- Ultraschnelle Photochemie (1)
- Vascularization (1)
- Verbindungen (1)
- Verbundwerkstoff (1)
- Vernetzung <Chemie> (1)
- Vernetzungsgrad (1)
- Wirkstoff (1)
- Wirkstoff-Träger-System (1)
- Wirkstoffdesign (1)
- Wirkstofffreisetzung (1)
- Xenobiotikum (1)
- Zerstörungsfreie Werkstoffprüfung (1)
- Zirkulardichroismus Spektroskopie (1)
- Zustandserkennung (1)
- abiotische (1)
- additive manufacturing (1)
- alloys (1)
- anodes (1)
- antibacterial (1)
- antibakteriell (1)
- batteries (1)
- biodegradable (1)
- biolayerinterferometry (1)
- bone (1)
- calciumhydroxide (1)
- cartilage (1)
- cathodes (1)
- chemoselective (1)
- chemosensitivity (1)
- chirality-sensitive spectroscopy (1)
- circular dichroism spectroscopy (1)
- coating (1)
- cofactorbinding (1)
- collagen (1)
- columnar phases (1)
- conjugated electrochromic polymers (1)
- covalent inhibition (1)
- cytochrome P450 enzymes, carboxylesterases, glutathione S-transferases (1)
- degradation (1)
- deposition (1)
- directional solidification (1)
- drug repurposing (1)
- electrochemistry (1)
- electrochromic device (1)
- eukaryotic gene expression (1)
- femtosecond spectroscopy (1)
- ferrocene (1)
- ferroelectrics (1)
- fluorescence (1)
- fragment screening (1)
- hydration dynamics (1)
- hydrophilic polymers (1)
- immunodrug delivery (1)
- implant (1)
- in silico models (1)
- in-vitro-assays (1)
- infrared-spectra (1)
- liquid crystal alignment (1)
- lithium-ion batteries (1)
- lung (1)
- lymph nodes (1)
- mRNA metabolism (1)
- nanoagent (1)
- nanogels (1)
- nanomateriales (1)
- nanotherapeutics (1)
- napthalene diimide (1)
- native chemical ligation (1)
- organic semiconductors (1)
- p97 (1)
- pICln (1)
- parallel polar dimers (1)
- plant extracts (1)
- polarimetry (1)
- poly(lactic-co-glycolic acid) (1)
- polycaprolactone (1)
- polycarbonates (1)
- protein hydration (1)
- protein-protein-interaction (1)
- scaffold (1)
- siliciumhaltige Synthesebausteine (1)
- subphthalocyanine (1)
- synthetic lethal interaction (1)
- synthetisch lethale Interaktion (1)
- trace elements (1)
- trans-formanilide (1)
- transient spectroscopy (1)
- triarylamine (1)
- uNMR (1)
- ultrafast photochemistry (1)
- umbrella-shaped mesogens (1)
- water migration (1)
- ß-Carbolinalkaloide, 7-Alkyloxycumarine, Clopidogrel, Paracetamol (1)
- ß-carboline alkaloids, 7-alkyloxycoumarins, clopidogrel, acetaminophen (1)
Institute
- Fakultät für Chemie und Pharmazie (44)
- Abteilung für Funktionswerkstoffe der Medizin und der Zahnheilkunde (10)
- Graduate School of Life Sciences (5)
- Institut für Pharmazie und Lebensmittelchemie (2)
- Fakultät für Physik und Astronomie (1)
- Graduate School of Science and Technology (1)
- Institut für Organische Chemie (1)
- Institut für Pharmakologie und Toxikologie (1)
- Klinik und Polikliniken für Zahn-, Mund- und Kieferkrankheiten (1)
- Theodor-Boveri-Institut für Biowissenschaften (1)
Sonstige beteiligte Institutionen
- Fraunhofer-Institut für Silicatforschung ISC (2)
- Fraunhofer Institute for Silicate Research ISC in Würzburg (1)
- Fraunhofer-Institut für Silicatforschung (ISC) in Würzburg (1)
- Institut für Optik und Atomare Physik, Technische Universität Berlin, 10623 Berlin, Germany (1)
- Laboratory for Chemistry and Life Science, Institute of Innovative Research, Tokyo Institute of Technology, Yokohama 226-8503, Japan (1)
- SKZ – Das Kunststoff-Zentrum (1)
ResearcherID
EU-Project number / Contract (GA) number
- 646737 (1)
The WHO-designated neglected-disease pathogen Chlamydia trachomatis (CT) is a gram-negative bacterium responsible for the most frequently diagnosed sexually transmitted infection worldwide. CT infections can lead to infertility, blindness and reactive arthritis, among others. CT acts as an infectious agent by its ability to evade the immune response of its host, which includes the impairment of the NF-κB mediated inflammatory response and the Mcl1 pro-apoptotic pathway through its deubiquitylating, deneddylating and transacetylating enzyme ChlaDUB1 (Cdu1). Expression of Cdu1 is also connected to host cell Golgi apparatus fragmentation, a key process in CT infections.
Cdu1 may this be an attractive drug target for the treatment of CT infections. However, a lead molecule for the development of novel potent inhibitors has been unknown so far. Sequence alignments and phylogenetic searches allocate Cdu1 in the CE clan of cysteine proteases. The adenovirus protease (adenain) also belongs to this clan and shares a high degree of structural similarity with Cdu1. Taking advantage of topological similarities between the active sites of Cdu1 and adenain, a target-hopping approach on a focused set of adenain inhibitors, developed at Novartis, has been pursued. The thereby identified cyano-pyrimidines represent the first active-site directed covalent reversible inhibitors for Cdu1. High-resolution crystal structures of Cdu1 in complex with the covalently bound cyano-pyrimidines as well as with its substrate ubiquitin have been elucidated. The structural data of this thesis, combined with enzymatic assays and covalent docking studies, provide valuable insights into Cdu1s activity, substrate recognition, active site pocket flexibility and potential hotspots for ligand interaction. Structure-informed drug design permitted the optimization of this cyano-pyrimidine based scaffold towards HJR108, the first molecule of its kind specifically designed to disrupt the function of Cdu1. The structures of potentially more potent and selective Cdu1 inhibitors are herein proposed.
This thesis provides important insights towards our understanding of the structural basis of ubiquitin recognition by Cdu1, and the basis to design highly specific Cdu1 covalent inhibitors.