The University of Basel is located in Basel, Switzerland, and is considered to be one of the leading universities in the country. In 2012, QS World University Rankings ranked the university 121st overall in the world, while two years before it was ranked 96–98th worldwide according to the Russian based Global University Ranking. In 2012, the ARWU ranked the university as the 85th best worldwide. Wikipedia.
University of Basel and PIQUR Therapeutics | Date: 2015-04-20
The invention relates to a method of manufacturing triazine, pyrimidine and pyridine derivatives of formula (I), wherein U, V, W and Z are nitrogen or carbon atoms, whereby at least one of U, V and W is nitrogen, and the other substituents are defined as in the specification, by condensing a corresponding halo-triazine, pyrimidine or pyridine in a type of Suzuki coupling with a pyridyl- or pyrimidinyl-borane, wherein the amino function is protected as a formamidine. The invention further relates to suitable intermediates and methods of manufacturing of such intermediates. Furthermore the invention relates to pure 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine in solid form.
Schubeler D.,Friedrich Miescher Institute for Biomedical Research |
Schubeler D.,University of Basel
Nature | Year: 2015
Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout. © 2015 Macmillan Publishers Limited.
Zimmerli W.,University of Basel
New England Journal of Medicine | Year: 2010
A 57-year-old man presents with fever, chills, and new lumbar back pain 2 weeks after undergoing a prostate biopsy because of an increased prostate-specific antigen level. His temperature is 39.7°C; he has an enlarged, tender prostate and lumbar spine tenderness. His white-cell count is 9100 per cubic millimeter, and the C-reactive protein level is 343 mg per liter. Urine and blood cultures reveal multidrug-resistant, extended-spectrum β-lactamase-producing Escherichia coli susceptible to imipenem. How should he be evaluated and treated? Copyright © 2010 Massachusetts Medical Society. All rights reserved.
Constable E.C.,University of Basel
Chemical Society Reviews | Year: 2013
Chirality is a concept that lies at the heart of organic chemistry but is often ignored in discussions of inorganic systems. This omission is all the more surprising, given the seminal role played by the study of chiral systems in the development of coordination chemistry. This tutorial review gives a brief introduction to the concept of chirality in coordination and supramolecular compounds for the non-specialist. © 2013 The Royal Society of Chemistry.
Wenger O.S.,University of Basel
Chemical Reviews | Year: 2013
The development of chemical sensors is a subject that continues to fascinate chemists in academic research. Aside from the purely academic interest, there is of course the important issue of finding suitable sensors for harmful chemical substances that might be present in the environment or at the workplaces. In addition, there is the phenomenon of luminescence vapochromism, often called vapoluminescence, which refers to changes in photoluminescence properties in the course of vapor exposure. The class of compounds in which these two closely related phenomena occur most frequently is undoubtedly the area of organometallic and coordination complexes. This review therefore focuses on transition-metal compounds that change color and/or their emission properties when exposed to VOCs. Hydrogen bond donation from methanol to the aminophosphine ligands may render the overall complex less flexible, making multiphonon relaxation less efficient.
Warburton R.J.,University of Basel
Nature Materials | Year: 2013
Self-assembled quantum dots have excellent photonic properties. For instance, a single quantum dot is a high-brightness, narrow-linewidth source of single photons. Furthermore, the environment of a single quantum dot can be tailored relatively easily using semiconductor heterostructure and post-growth processing techniques, enabling electrical control of the quantum dot charge and control over the photonic modes with which the quantum dot interacts. A single electron or hole trapped inside a quantum dot has spintronics applications. Although the spin dephasing is rather rapid, a single spin can be manipulated using optical techniques on subnanosecond timescales. Optical experiments are also providing new insights into old issues, such as the central spin problem. This Review provides a snapshot of this active field, with some indications for the future. It covers the basic materials and optical properties of single quantum dots, techniques for initializing, manipulating and reading out single spin qubits, and the mechanisms that limit the electron-spin and hole-spin coherence. © 2013 Macmillan Publishers Limited. All rights reserved.
Ward T.R.,University of Basel
Accounts of Chemical Research | Year: 2011
Artificial metalloenzymes are created by incorporating an organometallic catalyst within a host protein. The resulting hybrid can thus provide access to the best features of two distinct, and often complementary, systems: homogeneous and enzymatic catalysts. The coenzyme may be positioned with covalent, dative, or supramolecular anchoring strategies. Although initial reports date to the late 1970s, artificial metalloenzymes for enantioselective catalysis have gained significant momentum only in the past decade, with the aim of complementing homogeneous, enzymatic, heterogeneous, and organic catalysts. Inspired by a visionary report by Wilson and Whitesides in 1978, we have exploited the potential of biotin - avidin technology in creating artificial metalloenzymes. Owing to the remarkable affinity of biotin for either avidin or streptavidin, covalent linking of a biotin anchor to a catalyst precursor ensures that, upon stoichiometric addition of (strept)avidin, the metal moiety is quantitatively incorporated within the host protein. In this Account, we review our progress in preparing and optimizing these artificial metalloenzymes, beginning with catalytic hydrogenation as a model and expanding from there. These artificial metalloenzymes can be optimized by both chemical (variation of the biotin - spacer - ligand moiety) and genetic (mutation of avidin or streptavidin) means. Such chemogenetic optimization schemes were applied to various enantioselective transformations. The reactions implemented thus far include the following: (i) The rhodium-diphosphine catalyzed hydrogenation of N-protected dehydroaminoacids (ee up to 95%); (ii) the palladium-diphosphine catalyzed allylic alkylation of 1,3-diphenylallylacetate (ee up to 95%); (iii) the ruthenium pianostool-catalyzed transfer hydrogenation of prochiral ketones (ee up to 97% for aryl-alkyl ketones and ee up to 90% for dialkyl ketones); (iv) the vanadyl-catalyzed oxidation of prochiral sulfides (ee up to 93%). A number of noteworthy features are reminiscent of homogeneous catalysis, including straightforward access to both enantiomers of the product, the broad substrate scope, organic solvent tolerance, and an accessible range of reactions that are typical of homogeneous catalysts. Enzyme-like features include access to genetic optimization, an aqueous medium as the preferred solvent, Michaelis - Menten behavior, and single-substrate derivatization. The X-ray characterization of artificial metalloenzymes provides fascinating insight into possible enantioselection mechanisms involving a well-defined second coordination sphere environment. Thus, such artificial metalloenzymes combine attractive features of both homogeneous and enzymatic kingdoms. In the spirit of surface borrowing, that is, modulating ligand affinity by harnessing existing protein surfaces, this strategy can be extended to selectively binding streptavidin-incorporated biotinylated ruthenium pianostool complexes to telomeric DNA. This application paves the way for chemical biology applications of artificial metalloenzymes. © 2010 American Chemical Society.
Wenger O.S.,University of Basel
Accounts of Chemical Research | Year: 2013
Proton-coupled electron transfer (PCET) plays a crucial role in many enzymatic reactions and is relevant for a variety of processes including water oxidation, nitrogen fixation, and carbon dioxide reduction. Much of the research on PCET has focused on transfers between molecules in their electronic ground states, but increasingly researchers are investigating PCET between photoexcited reactants. This Account describes recent studies of excited-state PCET with d6 metal complexes emphasizing work performed in my laboratory.Upon photoexcitation, some complexes release an electron and a proton to benzoquinone reaction partners. Others act as combined electron-proton acceptors in the presence of phenols. As a result, we can investigate photoinduced PCET involving electron and proton transfer in a given direction, a process that resembles hydrogen-atom transfer (HAT). In other studies, the photoexcited metal complexes merely serve as electron donors or electron acceptors because the proton donating and accepting sites are located on other parts of the molecular PCET ensemble. We and others have used this multisite design to explore so-called bidirectional PCET which occurs in many enzymes. A central question in all of these studies is whether concerted proton-electron transfer (CPET) can compete kinetically with sequential electron and proton transfer steps.Short laser pulses can trigger excited-state PCET, making it possible to investigate rapid reactions. Luminescence spectroscopy is a convenient tool for monitoring PCET, but unambiguous identification of reaction products can require a combination of luminescence spectroscopy and transient absorption spectroscopy. Nevertheless, in some cases, distinguishing between PCET photoproducts and reaction products formed by simple photoinduced electron transfer (ET) (reactions that don't include proton transfer) is tricky. Some of the studies presented here deal directly with this important problem.In one case study we employed a cyclometalated iridium(III) complex. Our other studies with ruthenium(II) complexes and phenols focused on systematic variations of the reaction free energies for the CPET, ET, and proton transfer (PT) steps to explore their influence on the overall PCET reaction. Still other work with rhenium(I) complexes concentrated on the question of how the electronic structure of the metal-to-ligand charge transfer (MLCT) excited states affects PCET. We used covalent rhenium(I)-phenol dyads to explore the influence of the electron donor-electron acceptor distance on bidirectional PCET. In covalent triarylamine-Ru(bpy)3 2+/Os(bpy)3 2+-anthraquinone triads (bpy = 2,2′-bipyridine), hydrogen-bond donating solvents significantly lengthened the lifetimes of photogenerated electron/hole pairs because of hydrogen-bonding to the quinone radical anion. Until now, comparatively few researchers have investigated this variation of PCET: the strengthening of H-bonds upon photoreduction. © 2013 American Chemical Society.
Shimobayashi M.,University of Basel |
Hall M.N.,University of Basel
Nature Reviews Molecular Cell Biology | Year: 2014
More than 20 years after its discovery, our understanding of target of rapamycin (TOR) signalling continues to grow. Recent global 'omics' studies have revealed physiological roles of mammalian TOR (mTOR) in protein, nucleotide and lipid synthesis. Furthermore, emerging evidence provides new insight into the control of mTOR by other pathways such as Hippo, WNT and Notch signalling. Together, this progress has expanded the list of downstream effectors and upstream regulators of mTOR signalling. © 2014 Macmillan Publishers Limited.
Heim M.H.,University of Basel
Journal of Hepatology | Year: 2013
Hepatitis C virus (HCV) infections become chronic in the majority of infected individuals, and chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma. The innate immune system is central to host-virus interactions during the entire natural course of the disease. The HCV NS3/4A protease efficiently cleaves and inactivates two important signaling molecules in the sensory pathways that react to HCV pathogen-associated molecular patterns (PAMPs) to induce interferons (IFNs), i.e., mitochondrial antiviral signaling protein (MAVS) and Toll-IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF). Despite this viral escape mechanism, the innate immune system strongly reacts to HCV within the first days after infection. The sensory pathways, the type(s) of IFNs involved and the cellular source of IFNs are largely unknown. After 4-8 weeks, HCV specific T cells are recruited to the liver. IFN-γ-stimulated genes get strongly expressed in the liver. In about 30% of patients, the virus is eliminated during the acute phase of the infection by T cell-mediated antiviral mechanisms. In the remaining 70% of patients, HCV persists for decades. During this phase, T cell-derived IFN-γ cannot be detected any more in liver biopsies. Instead, in about half of the patients, hundreds of type I or III IFN-stimulated genes become again strongly expressed. However, this innate immune reaction is ineffective against HCV. Moreover, patients with constitutive IFN-stimulated gene (ISG) expression have a poor response to treatment with pegylated IFN-α (PegIFN-α) and ribavirin. The viral escape mechanisms that protect HCV from IFN-mediated innate immune reactions are not entirely understood, but might involve blockade of ISG protein translation at the ribosome, localization of viral replication to cells with refractory IFN signal transduction pathways or to cell compartments that are not accessible to antiviral IFN-stimulated effector systems. Recently, genetic variations near the IL28B (IFN-λ3) were found to be strongly associated with spontaneous clearance of HCV and response to treatment with PegIFN-α and ribavirin. The finding supports a central role of the innate immune response in host-viral interactions. The signaling pathways that link genetic variants of IL28B with immune answers to HCV remain to be elucidated. The present review article attempts to summarize current knowledge of some central aspects of the interactions of HCV with the innate immune system.