The discovery of novel and unique target−drug pairs for the treatment of human diseases such as cancer and bacterial infections is an urgent goal of chemical and pharmaceutical sciences. Natural products represent an inspiring source of compounds for designing chemical biology methods with applications in target identification and characterization. Inspired by ...

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5–Hydroxymethylcytosine (hmC) was recently detected as the sixth base in mammalian tissue at so far controversial levels. The function of the modified base is currently unknown, but it is certain that the base is generated from 5-methylcytosine (mC). This fuels the hypothesis that it represents an intermediate of an active demethylation process, which could ...

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IspG protein serves as the penultimate enzyme of the recently discovered non-mevalonate pathway for the biosynthesis of the universal isoprenoid precursors, isopentenyl diphosphate and dimethylallyl diphosphate. The enzyme catalyzes the reductive ring opening of 2C-methyl-d-erythritol 2,4-cyclodiphosphate, which affords 1-hydroxy-2-methyl-2-(E)-butenyl ...

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The proteasome's participation in essential biological processes such as stress response, cell proliferation, apoptosis, and antigen presentation has been well established.[1] It is, therefore, not surprising that academia and the pharmaceutical industry have made efforts to develop a range of small synthetic inhibitors against this proteolytic molecular machine ...

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The filter-aided sample preparation (FASP) method allows gel-free processing of biological samples sol- ubilized with detergents for proteomic analysis by mass spectrometry. In FASP detergents are removed by ultrafiltration, and after protein digestion peptides are separated from undigested material. Here we compare the effectiveness of different filtration ...

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A synthetic strategy toward maoecrystal V has been identified. It has been shaped by the necessity to maneuver in sterically hindered molecular environments.  

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Heterocyclic aromatic amines produce bulky C8 guanine lesions in vivo, which interfere and disrupt DNA and RNA synthesis. These lesions are consequently strong replication blocks. In addition bulky adducts give rise to point and frameshift mutations. The translesion synthesis (TLS) DNA polymerase Eta is able to bypass slowly C8 bulky adduct lesions such as the ...

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Ferredoxin:NADPH oxidoreductase (FNR) is a key enzyme of photosynthetic electron transport required for generation of reduction equivalents. Recently, two proteins were found to be involved in membrane-anchoring of FNR by specific interaction via a conserved Ser/Pro-rich motif: Tic62 and Trol. Our crystallographic study reveals that the FNR-binding motif, which ...

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Large scale phosphorylation analysis is more and more getting into focus of proteomic research. While it is now possible to identify thousands of phosphorylated peptides in a biological system, confident site localization remains challenging. Here we validate the Mascot Delta Score (MD score) as a simple method that achieves similar sensitivity and specificity ...

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The transmembrane domains (TMDs) of membrane-fusogenic proteins contain an overabundance of b-branched residues. In a previous effort to systematically study the relation among valine content, fusogenicity, and helix dynamics, we developed model TMDs that we termed LV-peptides. The content and position of valine in LV-peptides determine their fusogenicity and ...

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Target analysis of acivicin derived 3-halodihydroisoxazoles scaffolds in living non-pathogenic and pathogenic bacteria.  

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The biosynthesis of natural products is a treasure trove of unusual reaction mechanisms. This Minireview summarizes recent work on the structure and mechanism of IspH protein, which catalyzes the reductive dehydroxylation of an allyl alcohol in a biosynthetic pathway leading to isoprenoid precursors.  

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The impact of structural biology on the design of ligands (agonists, antagonists and modulators) for ionotropic glutamate receptors is reviewed.

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CIPSM spin-off AVIRU stands for anti virulence and is a biotechnology start-up that is currently funded as an EXIST transfer of technology project by the German Federal Ministry of Economics and Technology in compliance with a resolution of the German Parliament. AVIRU aims to develop the proof-of-concept for an innovative anti-infective drug for the treatment of ...

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Although there are potent antimalarial drugs available, the spread of drug resistance has led to an increase in morbidity and mortality rates in malaria-endemic regions. To overcome these problems, new antimalarial drugs with novel modes of action have to be developed. The recently discovered nonmevalonate pathway of isoprenoid biosynthesis (MEP pathway) is an ...

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The ubiquitin-proteasome system (UPS) is responsible for the controlled degradation of proteins in eukaryotic cells through conjugation of ubiquitin molecules and subsequent cleavage by a multimeric protein complex known as the 26S proteasome. Proteolysis occurs within the 20S proteasome core particle (CP), a large barrel-shaped protein complex composed of four ...

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The first total synthesis of newbouldine has been achieved employing a new, reductive N - N bond forming reaction. The asymmetric synthesis confirms that the natural product is a racemate.

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Diels–Alder reactions of vinyl quinones may provide a rapid entry to highly functionalized bi- and polycyclic ring systems. They involve the inverse-electron-demand cycloaddition of a suitable dienophile to a vinyl quinone, which presumably generates an “isoquinone methide” (Scheme 1). This reactive intermediate could then tautomerize in several ways to yield ...

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LC-MS has allowed the amount of the post-replicatively formed DNA base 5-hydroxymethylcytosine (see picture; left) to be quantified in brain tissue. The nucleoside is most abundant in areas that are associated with higher cognitive functions, and its content in mouse hippocampi seems to increase with age. The new method enables hydroxymethylcytosine to be ...

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A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring-closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various ...

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The evolution of mass spectrometry–based proteomic technologies has advanced our understanding of the complex and dynamic nature of proteomes while concurrently revealing that no ‘one-size-fits-all’ proteomic strategy can be used to address all biological questions. Whereas some techniques, such as those for analyzing protein complexes, have matured and are ...

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CIPSM spin-off XL-protein with its revolutionary PASylation technology has been awarded the Science4Life Venture Cup 2010 for its excellent business concept for the development of novel biologics with prolonged action. XL-biologics, a spin-off of XL-protein, will focus on the development of superior biopharmaceuticals with extended plasma half-life utilising the ...

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Glycoside hydrolases represent a large class of enzymes that cleave carbohydrate motifs. Since some enzymes play crucial roles in bacterial resistance pathways, we here introduce the synthesis and application of small sugar-based probes to study the function of the glycoside hydrolase NagZ.

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The heart of the ubiquitin-mediated degradation pathway, the 26S proteasome, endoproteolytically cleaves most intracellular proteins, thereby maintaining biological homeostasis and regulating many crucial processes in the cell. This hydrolyzing machine comprises more than 30 different subunits, which perform different functions including the recognition, ...

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In order to amaze our next generations for science and chemistry in particular, CIPSM hosted a two day event at an elementary school with lots of do-it-yourself experiments for the school kids. On the first day (11th of May) Oliver Baron gave an experimentary lecture with lots of explosions and "magical" reactions at the Department of Chemistry of the LMU for ...

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Tissue samples in biobanks are typically formalin-fixed and paraffin-embedded (FFPE), in which form they are preserved for decades. It has only recently been shown that proteins in FFPE tissues can be identified by mass spectrometry-based proteomics but analysis of post-translational modifications is thought to be difficult or impossible. The filter aided sample ...

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CIPSM hosts a two day event at an elementary school with lots of do-it-yourself experiments for the school kids. On the first day (11th of May) Oliver Baron gives a experimentary lecture at the Department of Chemistry of the LMU for around 300 kids focusing on water and matter in general. The following day the kids can experiment themselves and get a first ...

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CIPSM speaker Thomas Carell was honored today by the Bavarian Prime Minister Horst Seehofer with the Cross of Merit on ribbon of the Federal Republic of Germany.

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Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click ...

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Taking advantage of the recently developed Filter Assisted Sample Preparation (FASP) method for sample preparation, we performed an in-depth analysis of phosphorylation sites in mouse brain. To maximize the number of detected phosphorylation sites, we fractionated proteins by size exclusion chromatography (SEC) or separated tryptic peptides on an anion exchanger ...

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Solutions of allyl indium reagents formed in the reactions of indium with allyl bromide and allyl iodide, respectively, in N,N-dimethylformamide, tetrahydrofuran, and water were analyzed by a combination of electrospray-ionization mass spectrometry, temperature-dependent 1H NMR spectroscopy, and electrical conductivity measurements. Additional mass spectrometric ...

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Activity-based protein profiling (ABPP) has matured into a standard method for the fast, sensitive, and selective identification of enzyme activity and inhibitors in proteomes. By using natural product based probes, the targets of many uncharacterized molecules can be easily identified in complex proteomes, and their exact function and mechanism of action ...

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Flipped out: The cisplatin-(1,3-GTG) adduct, a strongly cytotoxic DNA lesion generated by the action of cisplatin therapeutics, is partially bypassed by Y-family DNA polymerase . Crystal structure data on this DNA-protein complex explain the partial-bypass process. The central dT unit of the lesion is turned out and blocks the movement of the enzyme along the DNA ...

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Small metal clusters fill the gap between the atomic scale and the metallic state with its distinctive bulk phenomena.[1] Besides being of high fundamental interest, this intermediate character of metal clusters also gives rise to unique and potentially useful electronic, magnetic, and optical properties.[ 2] To bring these properties to real-world applications, ...

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Repair of the Dewar valence isomers by (6-4) photolyases proceeds via an enzyme catalyzed ring-opening reaction of the Dewar lesion to the (6-4) photoproduct.

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Isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) represent the two central intermediates in the biosynthesis of isoprenoids. The recently discovered deoxyxylulose 5-phosphate pathway generates a mixture of IPP and DMAPP in its final step by reductive dehydroxylation of 1-hydroxy-2-methyl-2-butenyl 4-diphosphate. This conversion is catalyzed by ...

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The transmembrane domains of fusion proteins areknownto beimportant for their fusogenic activity. Inaneffort to systematically investigate the structure/function relationships of transmembrane domains we had previously designed LV-peptides that mimic natural fusion proteinTMDsin their ability to drive fusion after incorporation into liposomalmembranes. ...

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