A5042615787- Cancer-related Molecular Pathways
- Microbial Natural Products and Biosynthesis
- Marine Sponges and Natural Products
- Bioactive Compounds and Antitumor Agents
- Microtubule and mitosis dynamics
- Synthesis and biological activity
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Monoclonal and Polyclonal Antibodies Research
- Quinazolinone synthesis and applications
- Computational Drug Discovery Methods
- Cancer Treatment and Pharmacology
- Fungal Biology and Applications
- Synthesis and Biological Activity
- HER2/EGFR in Cancer Research
- Ubiquitin and proteasome pathways
- Molecular Biology Techniques and Applications
- Melanoma and MAPK Pathways
- Synthesis and Reactivity of Heterocycles
- RNA modifications and cancer
- Biochemical and Molecular Research
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- X-ray Diffraction in Crystallography
- Biological Research and Disease Studies
Reaction Biology (Germany)
2021-2024
University of Freiburg
2017-2018
University Medical Center Freiburg
2013
Technische Universität Braunschweig
2006-2012
Amsterdam UMC Location Vrije Universiteit Amsterdam
2010
University of Strathclyde
2009
Helmholtz Centre for Infection Research
2008-2009
Heinrich Heine University Düsseldorf
2008-2009
University of Vienna
2009
University of Perugia
2009
The p53 tumor suppressor protein can be phosphorylated at several sites within the N- and C-terminal domains, kinases have been shown to phosphorylate in vitro. In this study, we examined activity of proteins with combined mutations all reported N-terminal phosphorylation (p53N-term), (p53C-term), or together (p53N/C-term). Each these mutant retained transcriptional transactivation functions, indicating that is not essential for p53, although a subtle contribution activation expression...
The p53 tumor suppressor protein is activated in cells response to DNA damage and prevents the replication of sustaining genetic by inducing a cell cycle arrest or apoptosis. Activation accompanied stabilization protein, resulting accumulation high levels within cell. normally degraded through proteasome following ubiquitination, although mechanisms which regulate this proteolysis normal how becomes stabilized are not well understood. We show here that can also be substrate for cleavage...
From the Egyptian medicinal plant Polygonum senegalense fungal endophyte Alternaria sp. was isolated. Extracts of fungus grown either in liquid culture or on solid rice media exhibited cytotoxic activity when tested vitro against L5178Y cells. Chromatographic separation extracts yielded 15 natural products, out which seven were new compounds, with both differing considerably regard to their secondary metabolites. Compounds 1, 2, 3, 6, and 7 showed EC50 values ranging from 1.7 7.8 µg/mL. When...
The stability of the p53 tumor suppressor protein is regulated by interaction with Mdm2, product a p53-inducible gene. Mdm2-targeted degradation depends on between two proteins and mediated proteasome. We show here that in addition to N-terminal Mdm2 binding domain, C terminus participates ability be degraded Mdm2. In contrast, alterations central DNA domain p53, which change conformation protein, do not abrogate sensitivity Mdm2-mediated degradation. importance C-terminal oligomerization...
The endophytic fungus Stemphylium globuliferum was isolated from stem tissues of the Moroccan medicinal plant Mentha pulegium. Extracts fungus, which grown on solid rice medium, exhibited considerable cytotoxicity when tested in vitro against L5178Y cells. Chemical investigation yielded five new secondary metabolites, alterporriol G (4) and its atropisomer H (5), altersolanol K (11), L (12), stemphypyrone (13), known compounds 6-O-methylalaternin (1), macrosporin (2), A (3), E (6), D (7),...
The cancer cell secretome has emerged as an attractive subproteome for discovery of candidate blood-based biomarkers. To choose the best performing workflow, we assessed performance three first-dimension separation strategies prior to nanoLC-MS/MS analysis: (1) 1D gel electrophoresis (1DGE), (2) peptide SCX chromatography, and (3) tC2 protein reversed phase chromatography. 1DGE using 4-12% gradient gels outperformed methods with respect number identified proteins (1092 vs 979 580,...
Abstract Enniatins are mycotoxins which have important impact on human health, e.g . as contaminants of cereals, but also discussed possible anticancer agents. We investigated toxic effects enniatins A1, B and B1 isolated from Fusarium tricinctum different cancer cell lines. The showed moderate activity in HepG2 C6 cells (EC 50 ‐values approximately 10–25 μM), were highly H4IIE 1–2.5 μM). In cells, all increased caspase 3/7 nuclear fragmentation markers for apoptotic death. Enniatin enniatin...
Abstract Protein kinases represent promising anticancer drug targets. We describe here the meriolins, a new family of inhibitors cyclin-dependent (CDK). Meriolins chemical structural hybrid between meridianins and variolins, two families kinase extracted from various marine invertebrates. Variolin B is currently in preclinical evaluation as an antitumor agent. A selectivity study done on 32 showed that, compared with variolin B, meriolins display enhanced specificity toward CDKs, marked...
In the course of searching for new p38α MAP kinase inhibitors, we found that regioisomeric switch from 3-(4-fluorophenyl)-4-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine to 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine led an almost complete loss inhibition, but they showed activity against important cancer kinases. Among tested derivatives, 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine (6a) exhibited best activity, with IC50 in nanomolar...
Chemical investigation of the sponge Dactylospongia metachromia afforded five new sesquiterpene aminoquinones (1–5), two benzoxazoles (6 and 7), known analogue 18-hydroxy-5-epi-hyrtiophenol (8), a glycerolipid. The structures all compounds were unambiguously elucidated by one- two-dimensional NMR MS analyses, as well comparison with literature. Compounds 1–5 showed potent cytotoxicity against mouse lymphoma cell line L5178Y IC50 values ranging from 1.1 to 3.7 μM. When tested in vitro for...
AIMS--To elucidate the fine specificities of antibodies MIB 1 and 3 additional monoclonal which also recognise Ki-67 protein (MIB 5, IND.64, JG-67-2a). METHODS--Different parts cDNA were expressed in Escherichia coli. Bacterial lysates separated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) blotted on to nitrocellulose. Additionally different peptides synthesised a membrane support (SPOT-Blot). The immunoreactivity with recombinant proteins immobilised synthetic...
To develop multikinase inhibitors with dual PLK1/VEGF-R2 inhibitory activity, the d-annulated 1-benzazepin-2-one scaffold present in paullone family of kinase was investigated as a general structure template suitable for anchoring annulated heterocycles at hinge region ATP binding site. For this purpose, indole substructure paullones replaced by other nitrogen containing heteroaromatics. The designed scaffolds were synthesized and tested on indicated kinases....
Abstract Chemical investigation of the ethyl acetate extract Corynespora cassiicola , isolated from leaf tissues Chinese mangrove medicinal plant Laguncularia racemosa yielded four new secondary metabolites, including three decalactones, xestodecalactones D–F ( 1 – 3 ) as well corynesidone C 4 ), in addition to known compounds. The structures compounds were determined on basis one‐ and two‐dimensional NMR spectroscopy by high‐resolution mass spectrometry. Absolute configurations optically...