Emil Fischer Center

Erlangen, Germany

Emil Fischer Center

Erlangen, Germany

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PubMed | Emil Fischer Center, Evotec, Institute of Organic Chemistry I, Johannes Gutenberg University Mainz and 2 more.
Type: | Journal: Antiviral research | Year: 2015

Infection with human cytomegalovirus (HCMV) is a serious medical problem, particularly in immunocompromised individuals and neonates. The success of standard antiviral therapy is hampered by low drug compatibility and induction of viral resistance. A novel strategy is based on the exploitation of cell-directed signaling inhibitors. The broad antiinfective drug artesunate (ART) offers additional therapeutic options such as oral bioavailability and low levels of toxic side-effects. Here, novel ART-derived compounds including dimers and trimers were synthesized showing further improvements over the parental drug. Antiviral activity and mechanistic aspects were determined leading to the following statements: (i) ART exerts antiviral activity towards human and animal herpesviruses, (ii) no induction of ART-resistant HCMV mutants occurred invitro, (iii) chemically modified derivatives of ART showed strongly enhanced anti-HCMV efficacy, (iv) NF-B reporter constructs, upregulated during HCMV replication, could be partially blocked by ART treatment, (v) ART activity analyzed in stable reporter cell clones indicated an inhibition of stimulated NF-B but not CREB pathway, (vi) solid-phase immobilized ART was able to bind to NF-B RelA/p65, and (vii) peptides within NF-B RelA/p65 represent candidates of ART binding as analyzed by in silico docking and mass spectrometry. These novel findings open new prospects for the future medical use of ART and ART-related drug candidates.


Mittelmaier S.,Emil Fischer Center | Funfrocken M.,Fresenius Medical Care Deutschland GmbH | Fenn D.,Fresenius Medical Care Deutschland GmbH | Fichert T.,Fresenius Medical Care Deutschland GmbH | Pischetsrieder M.,Emil Fischer Center
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

Glucose degradation products (GDPs) formed during heat sterilization of peritoneal dialysis (PD) fluids exert cytotoxic effects and promote the formation of advanced glycation end-products in the peritoneal cavity. As a result, long-term application of continuous ambulatory peritoneal dialysis is limited. The composition and concentration of GDPs in PD fluids must be known to evaluate their biological effects. The present study describes a targeted screening for novel GDPs in PD fluids. For this purpose, dicarbonyl compounds were converted with o-phenylenediamine to give the respective quinoxaline derivatives, which were selectively monitored by HPLC/diode array detector. Glucosone was thereby identified as a novel major GDP in PD fluids. Product identity was confirmed by LC/MSMS analysis using independently synthesized glucosone as a reference compound. Furthermore, a method was developed to quantify glucosone in PD fluids by HPLC/UV after derivatization with o-phenylenediamine. The method's limit of detection was 0.6 μM and the limit of quantitation 1.1 μM. A linear calibration curve was obtained between 1.1 and 113.9 μM (R2 = 0.9999). Analyzed at three different concentration levels, recovery varied between 95.6% and 102.0%. The coefficient of variation ranged between 0.4% and 4.7%. The method was then applied to the measurement of glucosone in typical PD fluids. Glucosone levels in double chamber bag PD fluids varied between not detectable and 6.7 μM. In single chamber bag fluids, glucosone levels ranged between 28.7 and 40.7 μM. © 2010 Elsevier B.V. All rights reserved.


Schneider N.,Emil Fischer Center | Becker C.-M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Pischetsrieder M.,Emil Fischer Center
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

The enzyme lysozyme is used as a preservative to prevent late blowing of ripened cheese, caused by Clostridium tyrobutyricum. Since the enzyme is extracted from hen egg white, lysozyme has to be declared on food product labels as a potential allergen. Here, a method is reported that combines immunocapture purification and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis for the detection of lysozyme in cheese samples. Cheese extracts were treated with magnetic particles coated with a monoclonal antibody directed against lysozyme. After immunocapture purification, lysozyme was detected by MALDI-TOF-MS. The limit of detection of the assay was about 5 mg/kg lysozyme in cheese. The method reliably distinguished between cheese samples which had been produced with and without lysozyme. Thus, the novel assay allows the reliable, sensitive, and specific detection of lysozyme in a food matrix. The assay could be easily adapted to other target peptides and proteins in complex food matrices and, therefore, has a broad application potential, e.g. for the analysis of allergens. © 2009 Elsevier B.V. All rights reserved.


Maschauer S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Einsiedel J.,Emil Fischer Center | Hocke C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hubner H.,Emil Fischer Center | And 4 more authors.
ACS Medicinal Chemistry Letters | Year: 2010

The neurotensin receptor subtype 1 (NTS1) represents an attractive molecular target for imaging various tumors. Positron emission tomography (PET) gained widespread importance due to its sensitivity. We combined the design of a metabolically stable neurotensin analogue with a 68Ga-radiolabeling approach. The 68Ga-labeled peptoid?peptide hybrid [68Ga]3 revealed high stability, specific tumor uptake (0.7%ID/g, 65 min p.i.), and advantageous biokinetics in vivo using HT29 tumor-bearing nude mice. Because of the ability to internalize into NTS1-expressing tumor cells, [68Ga]3 proved to be highly suitable for a reliable and practical visualization of NTS1-expressing tumors in vivo by small animal PET. © 2010 American Chemical Society.

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