Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 04/06

Wed, 8 May 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15738/ https://edoc.ub.uni-muenchen.de/15738/1/Wirnhier_Eva_Antonie.pdf Wirnhier, Eva Antonie ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 30 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15996/ https://edoc.ub.uni-muenchen.de/15996/1/Willibald_Julian.pdf Willibald, Julian ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Mon, 29 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16525/ https://edoc.ub.uni-muenchen.de/16525/1/Reiter_Alwin.pdf Reiter, Alwin ddc:540, ddc:500, Fakultät für Chemie und Pharmazie 0

Wed, 24 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15702/ https://edoc.ub.uni-muenchen.de/15702/1/Tandon_Raman.pdf Tandon, Raman ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Thu, 18 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15709/ https://edoc.ub.uni-muenchen.de/15709/1/Boecklein_Sebastian.pdf Böcklein, Sebastian ddc:540, ddc:500

Thu, 18 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16205/ https://edoc.ub.uni-muenchen.de/16205/1/Pfaff_Janina.pdf Pfaff, Janina Michelle ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 16 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15710/ https://edoc.ub.uni-muenchen.de/15710/1/Berkenhoff_Kristine.pdf Berkenhoff, Kristine ddc:540, ddc:500, Fakultät für

Tue, 16 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16964/ https://edoc.ub.uni-muenchen.de/16964/1/Hinterholzinger_Florian.pdf Hinterholzinger, Florian ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

The Ski2-Ski3-Ski8 (SKI) complex is a conserved multi-protein assembly required for the cytoplasmic functions of the exosome, including messenger RNA (mRNA) turnover, surveillance and interference. The helicase Ski2, the tetratricopeptide repeat (TPR) protein Ski3 and the �-propeller Ski8 assemble in a heterotetramer with 1:1:2 stoichiometry. While the function of the Ski2-Ski3-Ski8 complex as a general cofactor of the cytoplasmic exosome has been well established, it remains largely unclear how it contributes to the regulation of the exosome. The PhD thesis at hand addresses this question by investigating the structural and biochemical properties of the Ski2-Ski3-Ski8 complex. Solving the crystal structure of the 113 kDa helicase region of S. cerevisiae Ski2 by experimental phasing revealed the presence of a canonical DExH core and an atypical accessory domain that is inserted in the helicase core. This insertion domain binds ribonucleic acid (RNA) unspeci�cally and is located at the RNA entry site of the helicase core. The overall architecture of Ski2 including the presence of an accessory domain is similar to the structure of the related helicase Mtr4, but the structural and biochemical properties of the accessory domains from both proteins are di�erent. The Ski2 insertion domain is not required for formation of the Ski2-Ski3-Ski8 complex. Its removal allowed to crystallize a Ski2�insert-Ski3-Ski8 complex from S. cerevisiae, and the crystal structure of this 370 kDa core complex was determined experimentally. It shows that Ski3 forms an array of 33 TPR motifs, creating a sca�old for the other subunits. Ski3 and the two Ski8 subunits bind the helicase core of Ski2 and position it centrally within the complex. This creates an extended internal RNA channel and modulates the enzymatic properties of the Ski2 helicase. Both Ski8 subunits are bound through a structurally conserved motif. A similar motif is present and functional in yeast Spo11, a protein that initiates deoxyribonucleic acid (DNA) double strand breaks during meiotic recombination. Association of Ski8 to either complex is mutually exclusive, rationalizing how Ski8 can perform its two distinct roles in mRNA metabolism and meiotic recombination. Biochemical studies suggest that the SKI complex can thread RNAs directly to the exosome, coupling the helicase and the exoribonuclease through a continuous channel of 43-44 nucleotides length. Finally, an internal regulatory mechanism in the Ski2-Ski3-Ski8 complex was identi�ed. Both the Ski2-insertion domain and the Ski3 N-terminus cooperate to inhibit ATPase and helicase activity of Ski2 when bound in the SKI complex. Thus, the SKI complex regulates exosome activity in two ways. First by a direct substrate channeling mechanism to the exosome that connects helicase and nuclease activities of both complexes which may activate the exosome towards certain substrates. Second, by an inhibitory mechanism that regulates substrate access to the helicase complex, which is a prerequisite for controlling the exosome's substrate speci�city. This doctoral thesis provides the �rst structural description of the entire yeast SKI complex and identi�es two mechanisms that may contribute to regulation of the activity of the cytoplasmic exosome.

Mon, 8 Apr 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15724/ https://edoc.ub.uni-muenchen.de/15724/1/Ruessmann_Florian.pdf Rüßmann, Florian ddc:540, ddc:500, Fakultät für Chemie und

Tue, 26 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16811/ https://edoc.ub.uni-muenchen.de/16811/1/Mandlmeier_Benjamin.pdf Mandlmeier, Benjamin ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 26 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16940/ https://edoc.ub.uni-muenchen.de/16940/1/Mirkovic-Hoesle_Milijana.pdf Mirkovic-Hösle, Milijana ddc:540, ddc:500, Fakultät

Mon, 25 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15860/ https://edoc.ub.uni-muenchen.de/15860/1/Junggeburth_Sebastian.pdf Junggeburth, Sebastian ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Carbon nitrides and carbon nitride derivatives are promising photocatalysts. The main focus of this thesis is the synthesis and characterization of various carbon nitrides (incompletely condensed melon, carbon nitride doped cesium titanate, ultra-long calcined melon, and OH-melem). Those carbon nitrides were then tested with regard to their photocatalytic properties. In the first part of chapter 3 of this thesis, we focus on a material called ‘‘melem oligomer’’. Two different synthesis routes were applied (open system and half open system) and the composition and structure of this material was studied. Melem with two different crystalline structures and some amorphous residues were found in the product. We also tested the photocatalytic activity of melem oligomer and confirmed hydrogen production from water with a relatively low rate of 2 μmol g-1 h-1. In the second part of chapter 3, we synthesized ultra-long calcined melamine which may have a morphology similar to the ‘‘g-C3N4 nanosheets’’. We analyzed both the composition and structure and investigated the efficiency of the presumed g-C3N4 nanosheets for hydrogen production from water. Ultra-long calcined melamine showed the best photoactivity which is twice that of melon at 490 °C. This is most likely due to the interesting morphology and high surface area. In chapter 4, melem oligomer was doped with cesium titanate in situ. Different calcination times were applied and various characterization techniques were used to investigate the composition, structure and morphology of the obtained materials. The efficiency of this hybrid photocatalyst for hydrogen production did not show higher photoactivity than the pure carbon nitrides except in the case of 16 h calcination which was the optimum calcination time overall. In chapter 5, OH-melem with a composition close to 2-oxo-6,10-diamino-s-heptazine, which could be a precursor of oxygen-doped g-C3N4, was synthesized and characterized by various techniques. Crystallinity is rather low in this oxygen containing species. NMR spectra differ from melem or cyameluric acid and XPS results confirm the presence of C=O groups. Overall, different carbon nitrides and carbon nitride derivatives were synthesized and chemically investigated to gain further knowledge on their synthesis, chemical properties and their resulting application as photocatalysts.

Fri, 22 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16774/ https://edoc.ub.uni-muenchen.de/16774/1/Moll_Richard.pdf Moll, Richard ddc:540, ddc:500, Fakultät für Chemie u

Fri, 22 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16977/ https://edoc.ub.uni-muenchen.de/16977/1/Loebermann_Florian.pdf Löbermann, Florian Wolfgang ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Thu, 21 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15899/ https://edoc.ub.uni-muenchen.de/15899/1/Mueller_Vesna.pdf Müller, Vesna ddc:540, ddc:500, Fakultät

The synthesis and properties of explosive urea and triazine derivatives is investigated on behalf of the explosive parameters and the full characterization of the molecules. (Chapter I-III) The class of oxadiazole derivatives is enhanced from the known explosive 1,2,5 oxadiazole (furazane) derivatives to the 1,2,4 oxadiazole derivatives. This molecule class is thoroughly investigated by all terms of chemical and explosive material matter and especially the 1,2,4-oxadiazol-5-one derivatives are compared to the corresponding tetrazole derivatives which were by far the most investigated molecule moiety of Prof. Dr. T.M. Klapoetke et al. for more than the last ten years. The 1,2,4 oxadiazol-5-one derivatives do only value as comparable model molecule to the tetrazole but were found to be good explosives themselves. So the triaminoguanidinium 1,2,4-oxadiazol-5-onate is suitable as low temperature propellant, the potassium and cesium 1,2,4-oxadiazol-5-onate are found to be good additions for NIR-flares and last but not least the best performing molecule was found to be the 3,5-diamino-1,2,4-oxadiazolium 5-aminotetrazolate, which combines the stability of the oxadiazole moiety with the very exothermic properties of a tetrazole in its best way. (Chapter IV-V) The 3-amino-1,2,4(4H)-oxadiazol-5-one is investigated thoroughly and detected to be a chemically and thermodynamically more stable system which can be functionalized according to methods known prior in the working group. The 3-dinitromethyl-1,2,4(4H)-oxadiazol-5-one is found a promising explosive class which can be combined as anion with a wide range of cations to tailor the stability and performance. The overall conclusion is that the 1,2,4-oxadiazole are chemical suitable as well as secondary explosives, propellants and pyrotechnics.

Mon, 4 Mar 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/18325/ https://edoc.ub.uni-muenchen.de/18325/1/Ruberg_Eva-Maria.pdf Ruberg, Eva-Maria ddc:540, ddc:500, Fa

DYNAMIC TRANSCRIPTOME ANALYSIS MEASURES RATES OF MRNA SYNTHESIS AND DECAY IN YEAST To obtain rates of mRNA synthesis and decay in yeast, we established dynamic transcriptome analysis (DTA). DTA combines non-perturbing metabolic RNA labeling with dynamic kinetic modeling. DTA reveals that most mRNA synthesis rates are around several transcripts per cell and cell cycle, and most mRNA half-lives range around a median of 11 min. DTA can monitor the cellular response to osmotic stress with higher sensitivity and temporal resolution than standard transcriptomics. In contrast to monotonically increasing total mRNA levels, DTA reveals three phases of the stress response. During the initial shock phase, mRNA synthesis and decay rates decrease globally, resulting in mRNA storage. During the subsequent induction phase, both rates increase for a subset of genes, resulting in production and rapid removal of stress-responsive mRNAs. During the recovery phase, decay rates are largely restored, whereas synthesis rates remain altered, apparently enabling growth at high salt concentration. Stress-induced changes in mRNA synthesis rates are predicted from gene occupancy with RNA polymerase II. Thus, DTA realistically monitors the dynamics in mRNA metabolism that underlie gene regulatory systems.

Mon, 25 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15554/ https://edoc.ub.uni-muenchen.de/15554/1/Gehring_Andre_P.pdf Gehring, André Philipe ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Mon, 25 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16607/ https://edoc.ub.uni-muenchen.de/16607/1/Weigand_Stefan.pdf Weigand, Stefan ddc:540, ddc:500, Fakultä

Mon, 25 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19313/ https://edoc.ub.uni-muenchen.de/19313/1/Moura_Linares_Elisangela.pdf Moura Linares, Elisângela ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Thu, 7 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15654/ https://edoc.ub.uni-muenchen.de/15654/1/Spalthoff_Veronika.pdf Spalthoff, Veronika Maria ddc:540, ddc:500, Fakultät fü

Wed, 6 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15389/ https://edoc.ub.uni-muenchen.de/15389/1/Piercey_Davin.pdf Piercey, Davin Glenn ddc:540, ddc:500, Fakultät für Chemie und Pharmazie 0

Tue, 5 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15343/ https://edoc.ub.uni-muenchen.de/15343/1/Troiber_Christina.pdf Troiber, Christina ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Fri, 1 Feb 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16599/ https://edoc.ub.uni-muenchen.de/16599/1/Seel_Stephanie.pdf Seel, Stephanie ddc:540, ddc:500, Fakultät

Tue, 29 Jan 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15365/ https://edoc.ub.uni-muenchen.de/15365/1/Virdi_Kulpreet_S.pdf Virdi, Kulpreet Singh ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Mon, 28 Jan 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16717/ https://edoc.ub.uni-muenchen.de/16717/1/Ameres_Stefanie_Maria.pdf Ameres, Stefanie ddc:540, ddc:500, Fakultät für Chemie und Phar

Thu, 24 Jan 2013 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17928/ https://edoc.ub.uni-muenchen.de/17928/1/Betzler_Franziska_Maria.pdf Betzler, Franziska Maria ddc:540, ddc:500, Fakultät für Chemie

Synthetic studies towards the total synthesis of the natural polyketide portentol. Synthetic studies to thiocarbonyl ylide based 1,3-dipoles. An efficient formal synthesis of dimethylglutamine via [3+2] cycloaddition of a thiocarbonyl ylide and subsequent Raney nickel reduction. Synthetic studies towards vinyl-quinone-Diels-Alder reactions. The first X-ray crystal structure of the Dess-Martin Periodinane

Wed, 19 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/17930/ https://edoc.ub.uni-muenchen.de/17930/1/Hofer_Alexander.pdf Hofer, Alexander ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 18 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15281/ https://edoc.ub.uni-muenchen.de/15281/1/Lindner_Christoph.pdf Lindner, Christoph ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 18 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15433/ https://edoc.ub.uni-muenchen.de/15433/1/Ammer_Johannes.pdf Ammer, Johannes ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Tue, 18 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15995/ https://edoc.ub.uni-muenchen.de/15995/1/Claus_Sarah.pdf Claus, Sarah ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

This dissertation describes the synthetic work on several natural products including nucleosides, alkaloids, and polyketides. The first and main part of this thesis focuses on the total synthesis of the nucleoside antibiotics herbicidin C and its hydrolysis product aureonuclemycin. Due to their diverse biological activity, the herbicidins are considered as promising herbicides for agricultural application. In cooperation with Bayer CropScience AG, a flexible and efficient access to the herbicidins was developed and the challenges and successes of this synthesis are described in detail. More specifically, the route to the undecose moiety integrates a stereoselective C-glycosylation with several reagent-controlled stereoselective transformations. The nucleobase was introduced by a surprisingly facile and highly diastereoselective late-stage N-glycosylation. In addition to that, natural herbicidin A was transformed into promising derivatives and all compounds, including the intermediates of the total synthesis, were provided to Bayer CropScience AG for a structure activity relationship study (SAR). A list of all provided derivatives is given at the end of the thesis. The progress toward the synthesis of stephadiamine is described in the second chapter of this thesis. The natural product is the first example of a C-norhasubanan alkaloid natural product and despite its structural beauty, no total synthesis of stephadiamine has been reported to date. The proposed racemic retrosynthetic analysis of stephadiamine makes use of a Curtius rearrangement and a late lactonization. The propellane skeleton of this alkaloid was envisioned to be made by means of a homoconjugated addition/Mannich cascade of the key enamine in an extremely efficient manner. An alternative strategy is proposed for future work, which includes a Tsuji-Trost allylation arising the potential for an enantioselective synthesis of stephadiamine. In chapter III, the progress toward the divergolides C and D is presented. Attention was focused on the large scale preparation of the volatile side chain, and its unusual isolation method is pointed out in detail. In addition, the assembly of the three main building blocks is discussed. The preparation of Legionella autoinducer 1 (LAI-1) is described in chapter IV. The bacterial signaling molecule LAI-1 belongs to the class of alpha-hydroxyketones (AHKs). Given the effects of LAI-1 on virulence and motility of the bacteria L. pneumophila, this signaling molecule has the potential for clinical or technical applications. For a deeper understanding of the signaling circuit in L. pneumophila and in order to gain more insight in the mechanism of cell-cell communication, synthetic LAI-1 was prepared and provided to the research group of H. Hilbi, who investigates the gene regulation by AHK-mediated signaling. Chapter V includes the experimental procedures for the preparation of all compounds, backed up by full analytical characterization. In addition, 1H- and 13C-NMR spectra as well as crystallographic details are given.

The rare alkali ion caesium (Cs+) is assimilated by eukaryotes, even though it is not an essential nutrient. It poses an environmental concern through the anthropogenic release of its radioisotopes, 134Cs and 137Cs. Bioavailability and long half-lives favour its uptake and accumulation in plants, via which radiocaesium can be introduced to the food chain. Cs+ ions are taken up via potassium-(K+)-related pathways due to the biophysical similarity of these cations. This makes it difficult to solely manipulate Cs+ accumulation in plants without disturbing the homeostasis of essential ions at the same time. This work shows that the soluble N-ethylmaleimide sensitive factor attachment receptor (SNARE) Sec22p, previously described as a member of the protein sorting machinery, specifically affects Cs+ accumulation in yeast by regulating the selectivity of vacuolar deposition. A similar phenotype became apparent for a homologous plant protein, SEC22. The loss of Saccharomyces cerevisiae Sec22p reduces Cs+ uptake by more than half, while at the same time leaving essential cations undisturbed. Mathematical modelling of wild-type and mutant Cs+ uptake kinetics proposes that sec22Δ is defective in vacuolar compartmentalisation of Cs+, which is proven by biochemical fractionation. Morphological alterations were not produced by the loss of Sec22p, only a Cs+-dependent vacuolar fragmentation can be observed. These results indicate a so far undescribed function of Sec22p in assuring a non-selective ion deposition to the vacuole, which is necessary in ion detoxification, while its loss induces discrimination against vacuolar Cs+ deposition. A developmentally controlled loss-of-function mutant of the orthologous gene SEC22 (At1g11890) in A. thaliana displays a similar phenotype, having specifically reduced Cs+ enrichment without detrimental growth defects, thereby translating the yeast findings to a multicellular context. Furthermore, a functional complementation of the yeast mutant Cs+ phenotype by the plant gene transcript was possible. Selective reduction of Cs+ accumulation in plants by loss of a single gene product represents a new route to limit radiocaesium input to the food chain without disturbing basic plant nutrition and growth.

Thu, 13 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15217/ https://edoc.ub.uni-muenchen.de/15217/1/Helfer_Stephanie.pdf Helfer, Stephanie ddc:540, ddc:500, Fakultät für Chem

Thu, 13 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15254/ https://edoc.ub.uni-muenchen.de/15254/1/Illi_Sarah.pdf Illi, Sarah ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Thu, 13 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16012/ https://edoc.ub.uni-muenchen.de/16012/1/Pfeiffer_Natalie_MV.pdf Pfeiffer, Natalie Verena Maria ddc:540, ddc:500, Fakultät für Chemie

Thu, 13 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19105/ https://edoc.ub.uni-muenchen.de/19105/1/Fischer_Niko.pdf Fischer, Niko ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Thu, 13 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/19107/ https://edoc.ub.uni-muenchen.de/19107/1/Scheutzow_Susanne.pdf Scheutzow, Susanne ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Wed, 12 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15523/ https://edoc.ub.uni-muenchen.de/15523/1/Stawski_Philipp.pdf Stawski, Philipp

Tue, 11 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15326/ https://edoc.ub.uni-muenchen.de/15326/1/Wolfgardt_Annette.pdf Wolfgardt, Annette ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Fri, 7 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16688/ https://edoc.ub.uni-muenchen.de/16688/1/Gerhold_Christian.pdf Gerhold, Christian-Benedikt ddc:540, ddc:500, Fakult

Wed, 5 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15135/ https://edoc.ub.uni-muenchen.de/15135/1/Culmes_Mihaela.pdf Culmes, Mihaela ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Wed, 5 Dec 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/16467/ https://edoc.ub.uni-muenchen.de/16467/1/Braun_Patricia.pdf Braun, Patricia Anna Maria ddc:540, ddc:500, Fakultät für Chemie und P

Fri, 30 Nov 2012 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/15182/ https://edoc.ub.uni-muenchen.de/15182/1/Chu_Yuanyuan.pdf Chu, Yuanyuan ddc:540, ddc:500, Fakultät für Chemie und Pharmazie

Most of the disulfuric acids like thiosulfuric acid (H2S2O3), dithionous acid (H2S2O4), disulfurous acid, (H2S2O5), dithionic acid (H2S2O6), disulfuric acid (H2S2O7) and peroxydisulfuric acid (H2S2O8) have never been obtained as pure compounds, because they are not stable at ambient temperatures. Therefore no experimental evidences are known for their structures. In this thesis, the synthesis and spectroscopical characterization of the disulfuric acids H2S2Ox (x = 3,4,6,8) is presented. The compounds were obtained by the reaction of dry Na2S2Ox or K2S2Ox with anhydrous HF at −60 °C. The protonated species H3S2Oy+MF6− (y = 3 - 8) were synthesized and characterized using the superacidic systems HF/MF5 (M = As, Sb). The protonation of sulfuric acid, (H3SO4+)n(GeF5−)n, with the new superacidic system HF/GeF4 is presented and gives evidence for the acid strength of this system. Moreover, the first single crystal structure of protonated dimethylsulfoxide (DMSO), [(CH3)2SOH+]4[Ge3F16]4− is discussed. The protonated forms of the aminosulfonic acids NH3SO3, NH3CH2SO3, NH3C2H4SO3 and methanesulfonamide (CH3SO2NH2) are described. In this context, the first crystal structure of protonated taurine, NH3C2H4SO3H+SbF6− is discussed.

Humane mesenchymale Stammzellen (hMSC) haben in den vergangenen Jahren auf-grund ihres potenziellen Einsatzes in der regenerativen Medizin sowie in der Prävention und Behandlung diverser Krankheiten ein großes wissenschaftliches Interesse geweckt. Einen wichtigen Aspekt stellt in diesem Zusammenhang die Regulation von Stammzell-funktionen durch Signalwege wie beispielsweise den Wnt/β-Catenin-Signaltransduk-tionsweg dar. Während am Signalweg beteiligte Komponenten und Teilfunktionen bereits beschrieben sind, existieren bezüglich der Initiation der Signaltransduktion an der Zelloberfläche auf Rezeptorebene lediglich rudimentäre Kenntnisse. Vor diesem Hintergrund wurde in dieser Arbeit die molekulare Funktion der Wnt-Ko-rezeptoren LRP5 und LRP6 (low-density lipoprotein receptor-related protein) im Wnt/β-Catenin-Signalweg von hMSC genauer untersucht. Für die spezifische Quantifizierung β-Catenin-abhängiger Transkriptionsprozesse wurde zunächst ein TCF/LEF-Reportergen-System in hMSC etabliert. In diesem System erfolgt die Expression des Reporterproteins erst nach Translokation von β-Catenin in den Zellkern und dessen Assoziation mit Transkriptionsfaktoren der TCF/LEF-Familie. Im Vergleich mit dem konventionellen TOP/FOP-Flash-Reportergen-System zeigte das TCF/LEF-Reportergen-System eine deutlich höhere Sensitivität. Mittels vergleichender Studien zur molekularen Funktion von LRP5 und LRP6, die neben der RNA-Interferenz (RNAi)-basierten Technologie auch Überexpressionsstudien und Rescue-Experimente beinhalteten, konnte eindeutig gezeigt werden, dass LRP6 eine entscheidende Rolle in der β-Catenin-vermittelten Signaltransduktion von hMSC übernimmt. Nach Applikation von Wnt-3a führte RNAi gegen LRP6 zu einer starken Ab-nahme der Wnt/β-Catenin-Signaltransduktion, wohingegen der Knockdown von LRP5 keine Veränderung zeigte. In einem umgekehrten Ansatz resultierte die Überexpression von LRP6 in einer starken Aktivierung des Wnt/β-Catenin-Weges, während die Über-expression von LRP5 keinen nachhaltigen Einfluss zeigte. Darüber hinaus führte in LRP6 -Knockdown-hMSC die Überexpression von LRP6 – jedoch nicht die von LRP5 – zur Rekonstitution der Wnt-3a-induzierten, β-Catenin-vermittelten Signaltransduktion. Diese Daten weisen LRP6 als den Hauptrezeptor für die Wnt-3a/β-Catenin-vermittelte Signaltransduktion in hMSC aus, wobei diese Funktion nicht durch LRP5 ersetzt werden kann. Da der Wnt/β-Catenin-Signalweg eng mit Differenzierungsprozessen assoziiert ist, wurde in diesem Kontext die Bedeutung der Wnt-Korezeptoren in hMSC evaluiert. Nach Knockdown von LRP6 war eine Differenzierung in die adipogene Richtung zu beobachten, die mit der Bildung fettähnlicher Vakuolen und einer erhöhten Expression des Transkriptionsfaktors PPAR-γ (Peroxisom-Proliferator-aktivierter Rezeptor-γ) assoziiert war. Unter dem Einsatz adipogener Zusätze konnte die Differenzierung von LRP6-Knockdown-hMSC in fettähnliche Zellen weiter verstärkt werden, was mit einer deutlich gesteigerten Akkumulation von Fettvakuolen sowie einer weiteren Erhöhung der PPAR-γ Expression einherging. Interessanterweise resultierte die Überexpression von LRP6 in diesen fettähnlichen Zellen in einer Zunahme der Wnt/β-Catenin-Signaltransduktion mit einer gleichzeitigen Abnahme der Expression von PPAR-γ. Zusammenfassend zeigen diese Erkenntnisse, dass LRP6 nicht nur in der Wnt-3a-induzierten, β-Catenin-vermittelten Signaltransduktion von hMSC eine tragende Rolle spielt, sondern auch für die Suppression der Differenzierung von hMSC in die adipogene Linie und damit für die Aufrechterhaltung des Stammzellcharakters entscheidend ist. Somit stellt der Wnt-Korezeptor LRP6 ein vielversprechendes Ziel zur therapeutischen Manipulation von hMSC in zukünftigen klinischen Anwendungen, wie z.B. der regenerativen und präventiven Medizin, dar.

Molecular chaperones of the Hsp70 class are essential for a number of cellular processes. The yeast mitochondrial Hsp70 chaperone Ssc1 plays an indispensable role for the mitochondrial biogenesis. As an essential component of the import motor of the TIM23 transolcase, Ssc1 drives the ATP-dependent translocation of proteins into the mitochondrial matrix. Moreover, it mediates the de novo folding and the assembly of several proteins in the mitochondrial matrix and prevents the formation of protein aggregates. Surprisingly, Ssc1 itself has a propensity to self-aggregate. Thus, it requires a helper protein, the chaperone Hep1 that prevents Ssc1 aggregation and maintains its structure and function. The mechanism of the protective function of Hep1 on Ssc1, however, is not understood. In the present study, the structural determinants of Ssc1 that make it prone to aggregation and the structural requirements of Ssc1 for its interaction with Hep1 were analysed and provided insights into the mechanism of prevention of Ssc1 aggregation by Hep1. The aggregation studies demonstrate that a variant of Ssc1 consisting of the ATPase domain and the subsequent interdomain linker aggregates in absence of Hep1. In contrast, the PBD and the ATPase domain alone are not prone to aggregation. Moreover, the interaction studies reveal that the aggregation-prone region seems to be the smallest entity within Ssc1 required for the interaction with Hep1. Taken together, the native Ssc1 adopts an aggregation-prone conformation, in which the ATPase domain with the interdomain linker has the propensity to aggregate. Hep1 binds to this aggregation-prone region and thereby counteracts the aggregation process and keeps the native Ssc1 in a functional and active state. Although Hsp70 chaperones are important for the biogenesis of a multitude of proteins, little is known about the biogenesis of these chaperones themselves. The present study reports on the analysis of the folding process of the mitochondrial Hsp70 chaperone Ssc1. In organello, in vivo and in vitro assays were established and then employed to study the de novo folding of Ssc1. Upon import into mitochondria, Ssc1 folds rapidly with the ATPase domain and the PBD adopting their structures independently of each other. Notably, the ATPase domain requires the presence of the interdomain linker for its folding, whereas the PBD folds without the linker. Moreover, in the absence of Hep1, the ATPase domain with the interdomain linker displays a severe folding defect, which indicates a role of Hep1 in the folding process of Ssc1. Apart from Hep1, none of the general mitochondrial chaperone systems seem to be important for the folding of Ssc1. Furthermore, the folding process of Ssc1 was reconstituted in vitro and the main steps of the folding pathway of Ssc1 were characterised. Hep1 and ATP/ADP are required and sufficient for the folding of Ssc1 into the native, catalytically active form. In an early step of folding, Hep1 interacts with the folding intermediate of Ssc1. This interaction induces conformational changes which allow binding of ATP/ADP. The binding of a nucleotide triggers Hep1 release and further folding of the intermediate into a native Ssc1. The present study provides the first direct evidence for the requirement of Hep1 for the folding of the Ssc1 chaperone. Thus, it demonstrates for the first time that the de novo folding of an Hsp70 chaperone depends on a specialized proteinaceous factor. In conclusion, Hep1 fulfils a dual chaperone function in the cell. It mediates the de novo folding of Ssc1 and maintains folded Ssc1 in a functional state during the ATPase cycle. Therefore, the Hep1 chaperone plays a crucial role for the protein biogenesis and homeostasis in mitochondria.