35 research outputs found

    Novel Wastewater Treatment Applications Using Polymeric Materials

    Get PDF
    This reprint focuses on the effective removal of organic and inorganic pollutants from water and wastewater using unique freestanding polymeric-based methods. It also examines innovative green methods for efficiently reusing various solid waste products. In addition, several new eco-friendly hybrid materials are being reviewed in order to alleviate the problem of water pollution in novel, rapid, and efficient methods

    Advances in Molecular Simulation

    Get PDF
    Molecular simulations are commonly used in physics, chemistry, biology, material science, engineering, and even medicine. This book provides a wide range of molecular simulation methods and their applications in various fields. It reflects the power of molecular simulation as an effective research tool. We hope that the presented results can provide an impetus for further fruitful studies

    Multiscale Molecular Dynamics Simulations of Histidine Kinase Activity

    Get PDF
    Zweikomponentensysteme (TCS), bestehend aus einer Sensorhistidinkinase (HK) und einem Antwortregulationsprotein, sind SchlĂŒsselbausteine in bakteriellen Signaluebertragungsmechanismen. Die FĂ€higkeit von Bakterien auf eine breite Vielfalt von chemischen und physikalischen Stimuli angemessen zu reagieren ist ausschlaggebend fĂŒr ihr Überleben. Es ist daher nicht ĂŒberraschend, dass TCS zu den meistuntersuchten bakteriellen Proteinsystemen gehört. Sensorhistidinkinasen sind typischerweise in die Zellmembran integrierte, homodimere Proteine bestehend aus mehreren DomĂ€nen. Reizwahrnehmung an der SensordomĂ€ne von HK löst eine Reihe von großskaligen KonformationsĂŒbergangen entlang der DomĂ€nen aus. WĂ€hrend sich die strukturellen Eigenschaften von verschiedenen HKs unterscheiden können, erhalten sie alle einen katalytischen ATP-bindenden Kern (CA) und dimerisierende HistidinphosphotransferdomĂ€nen (DHp). WĂ€hrend der Signalkaskade nimmt der Kern eine asymmetrische Konformation an, sodass die Kinase an einem der Protomere aktiv ist und die der anderen inaktiv. Das ermöglicht es dem ATP in einer der CA-DomĂ€nen seine Îł\gamma-Phosphatgruppe an das Histidin der DHp abzugeben. Diese Phosphorylgrouppe wird anschließend an das Antwortregulationsprotein weitergegeben, die eine angemessene Reaktion der Zelle veranlasst. In der vorliegenden Arbeit untersuche ich die Konformationsdynamik des Kinasekerns mithilfe von Molekulardynamiksimulationen (MD). Der Fokus der Arbeit liegt auf zwei verschiedenen HKs: WalK und CpxA. Wegen der GrĂ¶ĂŸe der Systeme und den erforderlichen biologischen Zeitskalen, ist es nicht möglich die relevanten KonformationsĂŒbergĂ€nge in klassischen MD-Simulationen zu berechnen. Um dieses Problem zu umgehen, verwende ich ein strukturbasiertes Modell mit paarweisen harmonischen Potentialen. Diese NĂ€herung erlaubt es, den Übergang zwischen dem inaktiven und den aktiven Zustand mit wesentlich geringerem rechnerischen Aufwand zu untersuchen. Nachdem ich das System mithilfe dieses vereinfachten Modells erkundet habe, benutze ich angereicherte Stichprobenverfahren mit atomistischen Modellen um detailliertere Einsichten in die Dynamik zu gewinnen. Die Ergebnisse in dieser Arbeit legen nahe, dass das Verhalten der einzelnen UnterdomĂ€nen des Kinasekerns eng miteinander gekoppelt ist

    Toxin-Antitoxin Systems in Pathogenic Bacteria

    Get PDF
    Bacterial toxin–antitoxin (TA) systems, which are ubiquitously present in bacterial genomes, are not essential for normal cell proliferation. The TA systems regulate fundamental cellular processes, facilitate survival under stress conditions, have essential roles in virulence and represent potential therapeutic targets. These genetic TA loci are also shown to be involved in the maintenance of successful multidrug-resistant mobile genetic elements. The TA systems are classified as types I to VI, according to the nature of the antitoxin and to the mode of toxin inhibition. Type II TA systems encode a labile antitoxin and its stable toxin; degradation of the antitoxin renders a free toxin, which is bacteriostatic by nature. A free toxin generates a reversible state with low metabolic activity (quiescence) by affecting important functions of bacterial cells such as transcription, translation, DNA replication, replication and cell-wall synthesis, biofilm formation, phage predation, the regulation of nucleotide pool, etc., whereas antitoxins are toxin inhibitors. Under stress conditions, the TA systems might form networks. To understand the basis of the unique response of TA systems to stress, the prime causes of the emergence of drug-resistant strains, and their contribution to therapy failure and the development of chronic and recurrent infections, must be known in order to grasp how TA systems contribute to the mechanisms of phenotypic heterogeneity and pathogenesis that will enable the rational development of new treatments for infections caused by pathogens

    Design, Functionalization, Synthesis and Evaluation of New Chiral Stationary Phases for (U)HPLC and Their Implementation in Drug Analysis, (Enantio)Purification and Structural Elucidation

    Get PDF
    Das Feld der chiralen FlĂŒssigchromatographie ist von herausragender Bedeutung fĂŒr eine Vielzahl akademischer und industrieller Anwendungen. Die Entwicklung neuer potenzieller Arzneistoffe, Umweltanalytik, laborgestĂŒtzte Diagnostik und StrukturaufklĂ€rung sind nur einige der Bereiche, aus denen die chirale FlĂŒssigchromatographie heute nicht wegzudenken ist. Aus diesem Grund gibt die vorliegende kumulative Dissertation einen Überblick sowohl ĂŒber die Entwicklung als auch ĂŒber die Anwendung chiraler stationĂ€rer Phasen fĂŒr die enantioselektive (Ultra-)HochleistungsflĂŒssigchromatographie ((U)HPLC). Im ersten Teil dieser Dissertation wuden neue chirale stationĂ€re Phasen (CSPs) basierend auf Anionentauschern und zwitterionischen Ionentauschern entwickelt. Folgende Ziele konnten dabei erreicht werden: Verschiedene Silikapartikel wurden bezĂŒglich ihrer kinetischen Leistung fĂŒr enantioselektive UHPLC optimiert. Dabei wurde ein detaillierter Einblick in die zahlreichen Interaktionsprozesse zwischen Analyt und stationĂ€rer Phase gewonnen [Publikation I]. Die Anbindungschemie und deren Entstehung durch chemische Radikalstarter (thermisch oder UV-initiiert) wurde verglichen und systematisch optimiert. Hier wurde eine neue, lösemittelfreie, UV-initiierte Immobilisierungsstrategie eingefĂŒhrt, welche zu wenig blutenden, sogenannten „Plattform-Typ“-Phasen fĂŒhrt [Publikation II]. Die Funktionalisierung von Silika, welche als Ausgangspunkt fĂŒr die Entwicklung CSP-basierter HPLC-SĂ€ulen gelten kann, wurde verĂ€ndert und fĂŒr schnelle Trennungen optimiert. Dies wurde durch eine Verringerung des Widerstands gegen den Massentransfer erreicht. Dazu wurden Silatrane verwendet, welche einen dĂŒnnen, homogenen Film an Thiolgruppen auf der OberflĂ€che der Silikapartikel formen. Hierzu wurde erst ein mehr- [Publikation III] und anschließend ein einstufiges Verfahren eingefĂŒhrt [Publikation IV]. Der zweite Teil der vorliegenden Dissertation handelt von der Anwendung chiraler Trennmethoden. Folgende Aspekte wurden dabei ausgearbeitet: Da die Anwendungsfelder der Metabolomik und Lipidomik nach immer mehr chiralen Trennmethoden verlangen, wurde ein Leitfaden zur Trennung verzweigter kurzkettiger FettsĂ€uren basierend auf PolysaccharidsĂ€ulen entwickelt [Publikation V]. Des Weiteren wurde die ChiralitĂ€t von vorher unbekannten Naturstoffen aufgeklĂ€rt [Publikation VI]. Ein Protokoll zur enantiomerenreinen Aufreinigung eines Radiotracers konnte entwickelt und angewandt werden [Publikation VII]. Das Wissen ĂŒber chirale HPLC-Trennungen sowohl im analytischen als auch im prĂ€parativen Maßstab wurde ferner in der Entwicklung neuer Wirkstoffkandidaten angewandt [Publikationen VIII und IX]. Zusammenfassend lĂ€sst sich sagen, dass eine umfassende Forschungsarbeit in dem Gebiet der Planung, Funktionalisierung, Synthese und Evaluierung chiraler stationĂ€rer Phasen sowie ihren breiten Anwendungsbereichen durchgefĂŒhrt wurde.Chiral liquid chromatography is a field of utmost importance for a wide range of academic and industrial applications. Drug development, environmental analysis, laboratory-based diagnostics, or structure elucidation among others, strongly rely on chiral liquid chromatography nowadays. For this reason, this cumulative thesis describes the development and applications of chiral stationary phases for enantioselective (ultra-)high performance liquid chromatography ((U)HPLC). In the first part of the thesis, new chiral stationary phases (CSPs) based on anion-exchange and zwitterionic ion exchange chiral selectors were developed. The following goals were achieved during the work on this thesis: Various silica particles were evaluated for their kinetic performance optimization for enantioselective UHPLC and a deep insight into a variety of interactions between analyte and stationary phase was gained [Publication I]. The bonding chemistry and its generation by thermic or UV-driven radical starter was evaluated and systematically optimized by introducing a solvent-free photo-click immobilization strategy resulting in low-bleeding, “platform-type” stationary phases [Publication II]. Furthermore, the functionalization of bare silica, which can be seen as the starting point of the production of a CSP-based HPLC column, was varied and optimized for fast separations by the reduction of mass transfer resistance using silatranes and thus forming thin, homogeneous monolayer of thiol functionalization in a multiple-step [Publication III] and in a single-step approach [Publication IV]. The second part of the thesis focuses on the application of enantiomer separation. This includes the elaboration of the following aspects: Since chiral methods are becoming increasingly important in the fields of metabolomics and lipidomics, a guide for the chiral analysis of branched short-chain fatty acids based on polysaccharide columns was developed [Publication V]. Furthermore, the chirality of previously unknown natural compounds was elucidated [Publication VI]. A protocol for the enantiopurification of a radiotracer was established [Publication VII]. Knowledge about chiral HPLC was used for both analytical and preparative separation in the development of potential new drugs [Publications VIII and IX]. In summary, extensive research on the design, functionalization, synthesis, and evaluation of chiral stationary phases and their scope of applications has been performed

    Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules

    Get PDF
    This book is a collection of papers published in the Special Issue of Pharmaceutics, entitled "Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules". A drug release profile is a consequential factor for nanoparticle application, directly related to drug stability and therapeutic results, as well as formulation development. Pharmaceutical particulates of different sizes and shapes (e.g., liposomes, oil-in-water emulsions, polymeric nano- and microspheres, metallic nanoparticles (NPs) such as gold, silver and iron oxide crystals, and core-shell hybrid NPs) offer many diagnostic and therapeutic applications. Membranes are also extensively utilized in many applications. They are especially beneficial to the distribution of macromolecular drugs and biopharmaceutical drugs (peptides, proteins, antibodies, oligonucleotides, plasmids, and viruses) with physicochemical and pharmacokinetic vulnerability. The delivery of drugs and bioactive molecules using particulates and membranes has gained a great deal of attention for various applications, such as the treatment of secondary infections, cancer treatment, skin regeneration, orthopaedic applications, and antimicrobial drug delivery. In addition, several production techniques have been utilized for the fabrication of particulates and membranes in the last decade, which include lyophilisation, micro-emulsion, nano-spray dryer, nano-electrospinning, slip casting and 3D printers. Therefore, pharmaceutical particulates and membranes possess excellent prospects to deliver drugs and bioactive molecules with the potential to improve new delivery strategies like sustained and controlled release

    Functionally Relevant Macromolecular Interactions of Disordered Proteins

    Get PDF
    Disordered proteins are relatively recent newcomers in protein science. They were first described in detail by Wright and Dyson, in their J. Mol. Biol. paper in 1999. First, it was generally thought for more than a decade that disordered proteins or disordered parts of proteins have different amino acid compositions than folded proteins, and various prediction methods were developed based on this principle. These methods were suitable for distinguishing between the disordered (unstructured) and structured proteins known at that time. In addition, they could predict the site where a folded protein binds to the disordered part of a protein, shaping the latter into a well-defined 3D structure. Recently, however, evidence has emerged for a new type of disordered protein family whose members can undergo coupled folding and binding without the involvement of any folded proteins. Instead, they interact with each other, stabilizing their structure via “mutual synergistic folding” and, surprisingly, they exhibit the same residue composition as the folded protein. Increasingly more examples have been found where disordered proteins interact with non-protein macromolecules, adding to the already large variety of protein–protein interactions. There is also a very new phenomenon when proteins are involved in phase separation, which can represent a weak but functionally important macromolecular interaction. These phenomena are presented and discussed in the chapters of this book

    Selected Papers from the 3rd International Symposium on Life Science

    Get PDF
    This book contains information for specialists in various fields of science. From the point of view of pharmacology, data are reported regarding the effect of echinochrome A and related metabolites from sea urchins on the survival and functional properties of stem cells, which can facilitate ex vivo application of this compound in medicine. For scientists who isolate and establish structures of marine natural compounds, an article devoted to the proof of the microbial origin of a typical metabolite earlier found exclusively from marine invertebrates, 6-epi-monanchorin, may also be of interest. A range of new marine metabolites was discovered from the both marine invertebrates and marine microorganisms, particularly in marine isolates of fungi. Some marine natural products could be applied to treat such diseases as Parkinson’s disease, ischemic stroke, viral infections, and so on. Magnificamide, a new peptide from sea anemones, inhibits porcine and human saliva amylases, showing its probable antidiabetic properties. Application of the genomic approach was discussed in studies on various marine bacteria, producing marine enzymes with unusual specificity. The lectins capable of recognizing glycoforms of different substrates demonstrate the possibility to be used to elaborate new medical diagnostics

    A Commemorative Issue in Honor of Professor Nick Hadjiliadis: Metal Complex Interactions with Nucleic Acids and/or DNA

    Get PDF
    This Special Issue of the International Journal of Molecular Science comprises a comprehensive study on “Metal Complex Interactions with Nucleic Acids and/or DNA”. This Special Issue has been inspired by the important contribution of Prof. Nick Hadjiliadis to the field of palladium or/and platinum/nucleic acid interactions. It covers a selection of recent research and review articles in the field of metal complex interactions with nucleic acids and/or DNA. Moreover, this Special Issue on "Metal Complexes Interactions with Nucleic Acids and/or DNA" provides an overview of this increasingly diverse field, presenting recent developments and the latest research with particular emphasis on metal-based drugs and metal ion toxicity
    corecore