Christoph Müller

Christoph Müller
Ludwig-Maximilians-University of Munich | LMU · Department of Pharmacy

Dr. rer. nat.

About

76
Publications
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720
Citations

Publications

Publications (76)
Article
Bats are strictly protected throughout Europe. They are a highly diverse order of mammals in terms of body size, body weight, migratory behaviour, trophic niche specialisation and habitat use. The latter ranges from urban areas and arable land to forest. Due to their low reproductive rate, environmental stressors can have a major impact on bat popu...
Preprint
Full-text available
A major limitation of current reports on insect declines is the lack of standardized, long-term, and taxonomically broad time series. Here, we demonstrate the utility of environmental DNA from archived leaf material to characterize plant-associated arthropod communities. We base our work on several multi-decadal leaf time series from tree canopies...
Conference Paper
Full-text available
Persistent organic pollutants, pesticides and biocides have a harmful impact on biological diversity. Besides short-term toxic effects on directly exposed organisms, they can have long-term effects resulting in changes of habitats and food chains. Their widespread use makes contact with pesticides and their residues inevitable for some wildlife. Ho...
Article
Full-text available
The aliphatic heterocycles piperidine and morpholine are core structures of well-known antifungals such as fenpropidin and fenpropimorph, commonly used as agrofungicides, and the related morpholine amorolfine is approved for the treatment of dermal mycoses in humans. Inspired by these lead structures, we describe here the synthesis and biological e...
Article
During the last decade, the understanding of the biological functions of cholesterol biosynthesis intermediates has changed significantly. Particularly, the enzyme sterol dehydrocholesterol reductase 24 (DHCR24) has taken center stage as a potential drug target. Inhibition of DHCR24 leads to accumulation of the endogenous, biologically active metab...
Article
Full-text available
Biosynthesis of sterols, which are key constituents of canonical eukaryotic membranes, requires molecular oxygen. Anaerobic protists and deep-branching anaerobic fungi are the only eukaryotes in which a mechanism for sterol-independent growth has been elucidated. In these organisms, tetrahymanol, formed through oxygen-independent cyclization of squ...
Article
In order to gain a better insight into pesticide and pollutant exposure of small (non-target) wildlife animals, a QuEChERS sample preparation method was first developed for 5 g liver tissues (e.g. hedgehog samples) and then downscaled for the analysis of 100 mg liver tissues (e.g. bat samples). The optimized (micro) QuEChERS methods used 1% acetic...
Preprint
Full-text available
Biosynthesis of sterols, which are key constituents of canonical eukaryotic membranes, requires molecular oxygen. Anaerobic protists and deep-branching anaerobic fungi are the only eukaryotes in which a mechanism for sterol-independent growth has been elucidated. In these organisms, tetrahymanol, formed through oxygen-independent cyclization of squ...
Article
Steroids play an important role in cell regulation and homeostasis. Many diseases like Alzheimer’s disease or Smith-Lemli-Opitz syndrome are known to be associated with deviations in the steroid profile. Most published methods only allow the analysis of small subgroups of steroids and cannot give an overview of the total steroid profile. We develop...
Article
In order to gain a better insight into pesticide and pollutant exposure in forests, a rapid and sensitive gas chromatorgraphy- tandem mass spectrometry (GC-MS/MS) method for the determination of 208 pesticide residues in leaves and needles has been established. The modified QuEChERS (quick, easy, cheap, effective, rugged and safe) approach uses 2 g...
Article
DMSO is widely used as powerful cryoprotectant for the storage and transport of frozen cells. Beyond this established application of DMSO, we could now show that it has also promising lyoprotectant effects in the field of lyophilisation of therapeutic cells. Freeze-drying of HaCaT keratinocytes in 10% HES, 5% HE and in presence of DMSO led to an in...
Article
The role of two-pore channel 2 (TPC2), one of the few cation channels localized on endolysosomal membranes, in cancer remains poorly understood. Here, we report that TPC2 knockout reduces proliferation of cancer cells in vitro, affects their energy metabolism, and successfully abrogates tumor growth in vivo. Concurrently, we have developed simplifi...
Article
Full-text available
In a project aimed at the further development of the potent steroidal anti‐inflammatory Δ24‐dehydrocholesterol reductase (DHCR24) inhibitor SH‐42 we worked out routes to ring B seco‐steroidal analogues. The required building blocks, bearing rings C and D of the parent steroidal structure, were synthesised starting from ergocalciferol. The novel sec...
Patent
The present invention relates to a method of preparing a barn dust extract, said barn dust extract, and a composition comprising said barn dust extract. The barn dust extract is useful in the prevention or treatment of a disease.
Article
Full-text available
Objectives: In this study, the pharmacological properties of six spirocyclic piperidines 1-6 showing very high σ1 receptor affinity (Ki = 0.2-16 nm) were investigated. Methods: In vitro receptor binding studies, retinal ganglion assay and in vivo capsaicin assay were used to determine the affinity, selectivity and activity. Influence on human tu...
Article
Targeting metabolism through bioactive key metabolites is an upcoming future therapeutic strategy. We questioned how modifying intracellular lipid metabolism could be a possible means for alleviating inflammation. Using a recently developed chemical probe (SH42), we inhibited distal cholesterol biosynthesis through selective inhibition of Δ ²⁴ -deh...
Article
Full-text available
In fungi, ergosterol is an essential component of the plasma membrane. Its biosynthesis from acetyl-CoA is the primary target of the most commonly used antifungal drugs. Here, we show that the pantothenate kinase Cab1p, which catalyzes the first step in the metabolism of pantothenic acid for CoA biosynthesis in budding yeast (Saccharomyces cerevisi...
Article
Distal cholesterol biosynthesis (CB) has recently taken center stage as a promising drug target in several diseases previously not linked to this biochemical pathway, including cardiovascular disease, cancer, multiple sclerosis and Alzheimer’s disease. Most enzymes involved in this pathway are hard to isolate, warranting dedicated analytical tools...
Article
Full-text available
Sulfoconjugates of sterols play important roles as neurosteroids, neurotransmitters, and ion channel ligands in health and disease. In most cases, sterol conjugate analysis is performed with liquid chromatography-mass spectrometry. This is a valuable tool for routine analytics with the advantage of direct sterol sulfates analysis without previous c...
Article
According to the European Pharmacopeia and the United States Pharmacopoeia dimethyl sulfoxide (DMSO) is a class 3 solvent and it is used in pharmaceutical industry amongst others as an additive for the lyophilisation process. DMSO has a very low vapour pressure and is therefore difficult to remove during freeze drying, with the result, that a signi...
Article
Full-text available
Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, res...
Article
Full-text available
Cytochrome P450 enzymes (P450) play essential roles in redox metabolism in all domains of life including detoxification reactions and sterol biosynthesis. The activity of P450s is fuelled by two electron-transferring mechanisms, heme-independent P450 reductase (CPR) and the heme-dependent cytochrome b5 (CYB5)/cytochrome b5 reductase (CB5R) system....
Article
Full-text available
Candida albicans is an inhabitant of mucosal surfaces in healthy individuals but also the most common cause of fungal nosocomial blood stream infections, associated with high morbidity and mortality. As such life-threatening infections often disseminate from superficial mucosal infections we aimed to study the use of probiotic Lactobacillus rhamnos...
Data
Generation of three-dimensional mucosal models. Summary of the different media used to generate three dimensional models of human oral mucosa. (DOC)
Data
Glucose content in KGM-Gold™ medium after 18 h in presence or absence of keratinocytes. The upper panel shows the amount of glucose in the supernatants of differentially treated monolayers of TR146 keratinocytes. In some cases the medium was supplemented with glucose (5 mg/ml). The lower panel shows the amount of glucose in KGM-Gold™ medium incubat...
Data
Three-dimensional mucosal model. Reconstructed human oral epithelium (RHOE) at day 8 of cultivation. (A) Semi-thin section stained with toluidine blue and visualized by light microscopy at a 400-fold magnification. (B) Ultra-thin sections were contrasted with osmium and visualized by transmission electron microscopy. Arrows indicate desmosomes. Sca...
Data
pH in the supernatant of differentially treated oral keratinocytes. (DOC)
Data
Differences between KGM-Gold™ medium and MRS medium. LGG (1.9 x 106 CFU/ml) and C. albicans (1 x 106 CFU/ml) were inoculated to KGM-Gold™ or MRS broth. OD600 was determined immediately and after 12 h incubation. pH was determined after 12 h incubation. To assess hyphal growth C. albicans was allowed to grow for 18 h. (DOC)
Data
Results of gene expression analysis in Candida albicans cultivated in epithelial cells in presence and absence of Lactobacillus rhamnosus GG. (A) Quantification of gene expression in C. albicans 2 h and 6 h post-infection. (B) Gene expression in C. albicans after 2 h of infection. (C) Gene expression in C. albicans after 6 h of infection. (XLS)
Article
Starting from enantiomerically pure amino acids, 1,4-diazepanes with various substituents in 1, 2, and 4-position were synthesized following the late stage diversification strategy. The key step in the formation of the seven-membered ring was the intramolecular EDC coupling of amino acids 15, 26, and 39. The configuration in 2-position does not inf...
Article
Cinnamon is a traditional herbal drug, but more importantly, it is used as a flavor compound in the production of foodstuff. Due to the content of significant concentrations of coumarin in Cassia cinnamon, effective control of the coumarin content in seasonal bakery products like ginger bread and cinnamon biscuits is urgently needed. Here we presen...
Article
Fungal infections and their increasing resistance to antibiotics are an emerging threat to public health. Novel antifungal drugs, as well technologies that can help us bolster the antimicrobial pipeline and understand resistance mechanisms, are needed. The ergosterol biosynthetic pathway is one potential target for antifungal drugs. Here we describ...
Article
Full-text available
A miniaturized QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Save) approach combined with gas chromatography–tandem mass spectrometry (GC–MS/MS) has been developed for the simultaneous determination of nine pesticides (Cyflufenamide, Difenoconazole, Dimethomorph, Fluopicolide, Fluopyram, Metrafenone, Myclobutanil, Quinoxyfen, and Tebuconazol...
Article
Combination products have become popular formats for the delivery of parenteral medications. Bake-on siliconization of glass syringes or cartridges allows good piston break-loose and gliding during injection at low silicone levels. Although widely implemented in industry, still little is known and published on the effect of the bake-on process on t...
Article
Azole drugs selectively target fungal sterol biosynthesis and are critical to our antifungal therapeutic arsenal. However, resistance to this class of drugs, particularly in the major human mould pathogen Aspergillus fumigatus, is emerging and reaching levels that have prompted some to suggest that there is a realistic probability that they will be...
Data
Effects of hapC deletion on fungal load in organs of immunosuppressed mice. (A) Cortisone acetate immunosuppressed OF-1 mice challenged intranasally with 1x105 CFU/animal of A. fumigatus. Horizontal bars represent the median. aP < 0.05 vs. wt, bP < 0.05 vs. hapCREC; (B) Cyclophosphamide immunosuppressed OF-1 mice challenged intravenously with 3x104...
Data
Characterisation of purified recombinant proteins used in this study. (A) SDS-PAGE analysis of wt (HapB/HapC/HapE) and mutated CBC (HapB/HapC/HapEP88L) as well as recombinant HapX(24–158) protein. (B) Analysis of the solution heterotrimeric state of HapB/C/E and HapB/C/EP88L complexes by analytical size exclusion chromatography coupled light scatte...
Data
ChIP-Seq Peaks from genes coding for enzymes of the ergosterol biosynthetic pathway. Cultures were grown for 18 h in AMM at 37°C. TSS, putative transcriptional start site. (DOCX)
Data
Alignment of the native (-293) and repeat region (-327TR) of the cyp51A promoter bound by the CBC with the A. nidulans cycA region whose structure was elucidated in complex with the AnCBC. Yellow highlights indicate bases conserved in all three binding sites, blue in two of the three. Underlined bases identify those outside the core domain shown to...
Data
Scheme of site-directed integration of plasmids for cyp51A promoter mutations and gfp-tagged hapC. (A) cyp51A based plasmids were linearised using BsrGI and transformed into Δcyp51A. The same transformation procedure was carried out for all plasmids containing modified cyp51A promoter versions. (B) Site-directed integration of a plasmid harboring C...
Data
Oligonucleotides used in this study (5´→3´). (DOCX)
Article
Full-text available
Therapeutic success of VEGF-based anti-angiogenic tumor therapy is limited due to resistance. Thus, new strategies for anti-angiogenic cancer therapy based on novel targets are urgently required. Our previous in vitro work suggested that small molecule Cdk5 inhibitors affect angiogenic processes such as endothelial migration and proliferation. More...
Article
The cyclization of oxidosqualene to lanosterol, catalyzed by the enzyme oxidosqualene cyclase (OSC), goes through a number of carbocationic high energy intermediates (HEI), and mimicking these intermediates is a promising approach for the development of OSC inhibitors. 3-Arylpiperidines (or tetrahydropyridines) were designed as steroidomimetic ring...
Article
Recent studies have highlighted the role of impaired barrier function and aberrant epithelial cell responses in the pathogenesis of allergy and asthma. Epidemiological studies showed that children growing up on farms have a lower incidence of childhood asthma, which was attributed to high microbial exposure. Interestingly, microbial exposure was fo...
Article
Inhibition of concise enzymes in ergosterol biosynthesis is one of the most prominent strategies for anti-fungal chemotherapy. Nevertheless, the enzymes sterol C5-desaturase and sterol C22-desaturase, which introduce double bonds into the sterol core and side chain, have not been fully investigated yet for their potential as antifungal drug targets...
Article
Fungal infections are a leading cause of morbidity and mortality for hospitalized patients, mainly because they remain difficult to diagnose and treat. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses only a restricted arsenal of antifungals is availabl...
Article
Inhibition of concise enzymes in ergosterol biosynthesis is one of the most prominent strategies for antifungal chemotherapy. Nevertheless, the enzymes sterol C5-desaturase and sterol C22-desaturase, which introduce double bonds into the sterol core and side chain, have not been fully investigated yet for their potential as antifungal drug targets....
Article
A method for the determination of phytosterols in herbal medicinal products for the treatment of lower urinary tract symptoms and food products is described here. Using a convenient sample preparation protocol and sensitive gas chromatography ion trap mass spectrometry analysis, ten different sterols, among them five Δ(7)-phytosterols as typical co...
Article
Full-text available
A series of novel N-alkyl tetra- and perhydroquinoline derivatives and their hydrochlorides were prepared from tetrahydro- or trans-perhydroquinoline by direct alkylation with alkyl halides and subsequent precipitation with HCl gas. The antimicrobial activity of the resulting amines was evaluated in an agar diffusion assay. The minimal inhibitory c...
Article
Full-text available
Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fi...
Article
A series of N-alkyl trans-decahydroisoquinoline, 1,2,3,4-tetrahydroisoquinoline, and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized starting from the respective secondary amines by N-alkylation with alkyl bromides. The compounds with C11 -alkyl chains showed antifungal potency comparable to clotrimazole, and inhibit enzym...
Article
Full-text available
During the last decade, our understanding about the function and biological activity of metabolites has drastically changed. Metabolites previously seen as sole bystanders of biochemical reactions without unique activity are becoming more and more recognized for their biological functions. One class of metabolites for which such a paradigm shift ha...
Article
Grundmann's ketone is converted to a spiroacetal containing a 5-hydroxymethyl-5-nitro-1,3-dioxane moiety whose hydroxymethyl group can be esterified or directly substituted with primary and secondary amines. Among the resulting aminomethyl spiroacetals, several ones bearing diamino residues were found to be inhibitors of the enzyme Δ8,7-isomerase i...
Article
Full-text available
A novel series of imidazol-5-yl carbinols and their 4-chlorobenzoyl esters has been synthesized by the Grignard reaction and subsequent esterification. These compounds were screened for their antimicrobial activities in an agar diffusion assay. The compounds with C10 to C12-alkyl side chains displayed significant antimycotic activity.
Article
A series of aminopropylindenes, designed as mimics of a cationic high energy intermediate in the oxidosqualene cyclase(1) (OSC)-mediated cyclization of 2,3-oxidosqualen to lanosterol was prepared from Grundmann's ketone. Screening on OSCs from five different organisms revealed interesting activities and selectivities of some of the compounds. A N,N...
Article
Increasing resistance of clinically relevant fungi is causing major problems in anti-mycotic therapy. Particularly for immunosuppressed patients fungal infections are of concern and increasing resistance against clinically used antimycotic drugs is hampering successful treatment. In the search for new antifungals ergosterol biosynthesis still is th...
Article
Starting from Grundmann's ketone a new chemotype of inhibitors of the post-squalene part of cholesterol biosynthesis was developed. Stereoselective introduction of an angular methyl group at C-3a, followed by a plethora of functionalisations at C-4 and C-5 led to cis-configured amino alcohols as a new chemotype of inhibitors of cholesterol biosynth...
Article
We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished...
Article
We prepared new phenethyltetrahydroisoquinolines, derivatives of plant isoquinoline alkaloids. Several of the compounds showed a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR), an enzyme responsible for the conversion of 7-DHC to cholesterol in the last step of cholesterol biosynthesis. A defect of 7-DHCR is associated w...
Article
Levels of nicotine higher than the maximum residue level were detected in edible mushrooms. Analyses of self-collected and purchased dried mushrooms were performed with a QuEChERS approach. A small amount (2.5g) of dried sample matrix was mixed with 5mL sodium hydroxide solution, 2.5g of sodium sulfate/sodium chloride mixture (4:1) and 5mL ethyl ac...

Projects

Projects (2)
Project
Dear colleagues, Franz Bracher and I am organizing, as guest editors, a Special Issue in "Synthesis and Bioanalysis of Steroids and Steroid Biosynthesis Inhibitors" for Molecules. Please find more information at https://www.mdpi.com/journal/molecules/special_issues/Steroids_Inhibitors Keywords Enzyme inhibitors (chemistry and pharmacology) Steroid analysis in diverse samples (tissues, plant material, screening systems) Biological activities and metabolism Steroid biosynthesis Synthesis of steroids and analogues Steroid isolation from diverse sources (mammals, plants, microorganisms)
Archived project
Environmental pollution is described as one underlying cause for population declines in reptiles and especially affects species in agricultural landscapes.