Role of WNT1-inducible signaling pathway protein-1 (WISP1) in liver injury See

Liver diseases are a global burden and a better understanding of factors controlling disease progression is required. In the last decade, much progress has been achieved in understanding the relevance of the extracellular matrix. Alterations in this dynamic structure can either facilitate or impair the repair of damaged liver tissue. Therefore, matricellular proteins of the CCN family, have emerged as new targets in liver pathophysiology. These highly conserved secreted proteins specifically ...

Identification and characterization of small molecules inducing cellular reactive oxygen species accumulation See

The human cell is constantly confronted with reactive oxygen species (ROS), which are oxygen-containing chemical intermediates readily reacting with different biomolecules. ROS can originate from exogenous sources, but are also produced within cells, e.g. as part of their metabolism. Depending on the concentration, ROS can either act as important signaling molecules or induce oxidative stress, thereby harming cellular components. Thus, cells utilize a multitude of antioxidant mechanisms to ma...

Rational design of metal-mediated DNA G-quadruplexes as DNAzymes See

Apart from the widely known duplex structure DNA can fold into various secondary structures such as hairpin loops, triplexes and G-quadruplexes. The latter self-assemble from guanine rich strands by Hoogsteen base pairing to form stacked guanine tetrads. Since their discovery, G-quadruplexes became increasingly interesting in the field of chemical biology due to their property to control the elongation of telomeres and the expression of oncogenes. Furthermore, first examples of a DNAzyme acti...

Dye-based coordination cages See

Synthetic organic dyes find broad use in industry (e.g. as colorizing agents and laser materials), medicine (e.g. as diagnostic tools and drugs) and research (e.g. in fluorescence microscopy, FRET setups and as photosensitizers). All the applications originate from the typical interaction that these chromophores have with visible light. However, while a number of these dyes is produced on a multi ton scale since decades, their implementation into complex chemical systems and nano structures s...

Coal-tar dye-based coordination cages and helicates See

A strategy to implement four members of the classic coal-tar dye family, Michler´s ketone, methylene blue, rhodamine B and crystal violet, into [Pd2L4] self-assemblies is introduced. Chromophores were incorporated into bis-monodentate ligands using piperazine linkers that allow to retain the auxochromic dialkyl amine functionalities required for intense colors deep in the visible spectrum. Upon palladium coordination, ligands with pyridine donors form lantern-shaped dinuclear cages while quin...

Backbone-bridging promotes diversity in heteroleptic cages See

The combination of shape-complementary bis-monodentate ligands LA and LB with PdII cations yields heteroleptic cages cis-[Pd2LA2LB2] by self-sorting. Herein, we report how such assemblies can be diversified by introduction of covalent backbone bridges between two LA units. Together with solvent and guest effects, the flexibility of these linkers can modulate nuclearity, topology, and number of cavities in a family of four structurally diverse assemblies. Ligand LA1, with flexible linker, reac...

Tripod-shaped organotin compounds: complexation studies towards Lewis bases and chalcogenido clusters of unprecedented nuclearity See

The principal axes of this thesis project are the synthesis of tripodal tris(organostannylmethyl)silanes of the type MeSi(CH2SnR(3–n)Xn)3 (n = 0– 3; X = I, F, Cl, Br; R = Ph, CH2SiMe3) , as building blocks for the synthesis of novel organostannate complexes and umprecedented organotin chlacogeno-clusters among which novel triangular belt-shaped diorganotin oxo clusters [MeSi(CH2SnRO)3]n, R = Ph, CH2SiMe3 with gigantic nuclearity; oktokaideka (n = 18) and trikonta (n = 30). Furthermore, format...

Collective information processing in synthetic morphogenic liposomes and hybrid cell-computer wound healing with optogenetically emulated signaling See

Throughout the different scales at which living organisms operate, it is the collective behaviour between the entities that compose them that determines their identity and function. Biomolecules, cells and whole organisms interact to process information and generate organization at the subcellular, tissue and ecosystem scales. In the first part of this thesis, we investigated fundamental principles of cellular morphogenesis in response to external cues in a Synthetic Morphogenic Membrane...

Stabilität und Aktivität ausgewählter Enzymsysteme unter extremen Umweltbedingungen See

In jedem Lebewesen findet eine Vielzahl verschiedener biochemischer Reaktionen statt, die durch Enzyme vermittelt werden. Angesichts verschiedener Vorteile gegenüber chemischen Katalysatoren besteht ein großes Interesse an der Verwendung solcher Biokatalysatoren in industriellen Prozessen. Um die Produktausbeute einer Reaktion bzw. katalytischen Eigenschaften eines Enzyms noch weiter zu optimieren, werden heutzutage mittels zielgerichtetem Proteindesign, Immobilisierungstechniken sowie durch ...

Einfluss natürlicher und synthetischer Lipide sowie verschiedener Cosolventien auf Lipidmembranen See

Durch die Entwicklung und Verwendung einfacher bis hin zu komplexen Modellsystemen aus elementaren und molekularen Grundbausteinen einer biologischen Zelle ermöglicht es die biophysikalische Chemie, Antworten zu einem breiten Spektrum an biologischen, chemischen und medizinischen Fragestellungen zu liefern sowie biologische und biochemische Prozesse unter kontrollierten Bedingungen und mit großen Ähnlichkeiten zu natürlichen Systemen zu untersuchen. Eine Grundlage vieler Lebensprozesse bilden...

Regulation of natural killer cell cytotoxic pathways during serial killing activity See

Natural Killer (NK) cells act as the front line of the body´s defense in the immune system and they are key players in efficiently recognizing and eliminating virus-infected and tumor cells. Individual NK cells can eliminate multiple target cells in a sequential manner during a process named serial killing. There are two major pathways NK cells use to induce apoptosis in their target cells: By releasing the content of cytotoxic granules containing the serine protease granzyme B (GrzB) and the...

A new mechanically-interlocked [Pd2L4] cage motif by dimerization of two peptide-based lemniscates See

Most metallo-supramolecular assemblies of low nuclearity adopt simple topologies, with bridging ligands spanning neighboring metal centers in a direct fashion. Here we contribute a new structural motif to the family of host compounds with low metal count (two) that consists of a pair of doubly-interlocked, figure-eight-shaped subunits, also termed “lemniscates”. Each metal is chelated by two chiral bidentate ligands, composed of a peptidic macrocycle that resembles a natural product with two ...

Alterations of the glyoxylate metabolism in hepatic steatosis – a risk factor for hyperoxaluria See

Non-alcoholic fatty liver disease (NAFLD) comprises a wide spectrum of liver diseases and is the leading cause of liver diseases worldwide. Features of the metabolic syndrome and extrahepatic diseases, like cardiovascular diseases and kidney stone disease, strongly associate with NAFLD. A previously identified steatosis-associated downregulation of the alanine-glyoxylate aminotransferase (AGXT) was suggested to be one molecular link explaining the connection of NAFLD with the development of c...

Light-Activatable TET-Dioxygenases Reveal Dynamics of 5-Methylcytosine Oxidation and Transcriptome Reorganization See

Ten-eleven-translocation (TET) dioxygenases catalyze the oxidation of 5-methylcytosine (5mC), the central epigenetic regulator of mammalian DNA. This activity dynamically reshapes the epigenome and transcriptome by depositing oxidized 5mC derivatives and initiating active DNA demethylation. However, studying this dynamic is hampered by the inability to selectively activate individual TETs with temporal control in cells. We report activation of TETs in mammalian cells by incorporation of genet...

Pressure sensitivity of SynGAP/PSD‐95 condensates as a model for postsynaptic densities and its biophysical and neurological ramifications See

Biomolecular condensates consisting of proteins and nucleic acids can serve critical biological functions—so much so that some condensates are referred as membrane‐less organelles. They can also be disease‐causing if their assembly is misregulated. A major physico‐chemical basis of the formation of biomolecular condensates is liquid‐liquid phase separation (LLPS). In general, LLPS depends on environmental variables such as temperature and hydrostatic pressure. We investigated the effects of p...

Dynamic complex-to-complex transformations of heterobimetallic systems influence the cage structure or spin state of iron(II) ions See

Two new heterobimetallic cages, atrigonal-bipyr-amidal and acubic one, were assembled from the same mononuclear metalloligand by adopting the molecular library approach,using iron(II) and palladium(II) building blocks. The ligand system was designed to readily assemble through subcomponent self-assembly. It allowed the introduction of steric strain at the iron(II) centres, which stabilizes its para-magnetic high-spin state.This steric strain was utilized to drive dynamic complex-to-complex tr...

Substrate and product binding inside a stimuli-responsive coordination cage acting as singlet oxygen photosensitizer See

An acridone-based, interpenetrated double cage [3BF4Pd4L8] acts as a photosensitizer for generating singlet oxygen which adds to 1,3-cyclohexadiene in a [2+4] hetero-Diels-Alder reaction to form 2,3-dioxabicyclo[2.2.2]oct-5-ene. Photocatalytic activity was exclusively observed for the assembled cage, whereas the free organic ligand L decomposes upon irradiation. While cage [3BF4Pd4L8] does not accept any organic guests, NMR, MS and single crystal X-ray results reveal that both substrate and p...

Synthese amphiphiler Blockcopolymere und deren Anwendung in der Nanopartikel-basierten Katalyse See

Die nachhaltige Gestaltung chemischer Prozesse vom Labor- bis zum Industriemaßstab unter Beachtung der Aspekte der Grünen Chemie ist ein Kernbestandteil moderner Syntheseplanung. Hierzu zählen neben der Katalyse an sich auch die Atomökonomie, Katalysatorrückgewinnung, Vermeidung von Abfallprodukten, die Verwendung günstiger und umweltfreundlicher Ausgangsstoffe und Lösungsmittel sowie Arbeitssicherheit. Um diese Punkte miteinander zu verbinden, wurden im Rahmen der vorliegenden Dissertation K...

Click-mediated enrichment of specific genomic loci See

In all organisms, the genetic information of cells is stored in the nucleotide sequence of deoxyribonucleic acid (DNA). The human organism consists of more than 200 different somatic cell types with the same genetic information (genotype). Even though, they drastically differ in their morphology and function (phenotype), which is related to different gene expression levels. Gene expression is controlled by macromolecular interactions and epigenetic modifications on chromatin that are highly l...