A5075772816- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- Biochemical and Structural Characterization
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Cancer-related gene regulation
- DNA and Nucleic Acid Chemistry
- Wnt/β-catenin signaling in development and cancer
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Antimicrobial Peptides and Activities
- Enzyme Catalysis and Immobilization
- Glycosylation and Glycoproteins Research
- PI3K/AKT/mTOR signaling in cancer
- Microtubule and mitosis dynamics
- Protein Structure and Dynamics
- Supramolecular Self-Assembly in Materials
- RNA modifications and cancer
- RNA Research and Splicing
- Bacteriophages and microbial interactions
- Cancer Mechanisms and Therapy
Vrije Universiteit Amsterdam
2016-2025
University of Göttingen
2025
Chemical Genomics Centre
2012-2023
Max Planck Society
2012-2023
TU Dortmund University
2014-2023
University of Würzburg
2023
Universitätsklinikum Würzburg
2023
Oncode Institute
2023
Ludwig-Maximilians-Universität München
2023
Technion – Israel Institute of Technology
2023
Aberrant activation of signaling by the Wnt pathway is strongly implicated in onset and progression numerous types cancer. Owing to persistent dependence these tumors on for growth survival, inhibition this considered an attractive mechanism-based therapeutic approach. Oncogenic can ensue from a variety distinct aberrations pathway, but most share common feature causing increased cellular levels β-catenin interfering with its constitutive degradation. β-Catenin serves as central hub engaging...
Crop yield loss due to flooding is a threat food security. Submergence-induced hypoxia in plants results stabilization of group VII ETHYLENE RESPONSE FACTORs (ERF-VIIs), which aid survival under these adverse conditions. ERF-VII stability controlled by the N-end rule pathway, proposes that N-terminal cysteine oxidation normoxia enables arginylation followed proteasomal degradation. The PLANT CYSTEINE OXIDASEs (PCOs) have been identified as catalysts this oxidation. presumably arises from...
A systematic study on cell penetration by stapled peptides.
Bioactive conformations of peptides can be stabilized by macrocyclization, resulting in increased target affinity and activity. Such macrocyclic proved useful as modulators biological functions, particular inhibitors protein-protein interactions (PPI). However, most peptide-derived PPI involve α-helices, leaving a large number secondary structures unaddressed. Herein, we present rational approach towards stabilization an irregular peptide structure, using hydrophobic cross-links that replace...
Herein we describe a novel DNA-catalyzed transfer of reporter group from donating to an accepting oligo-peptide nucleic acid (PNA), generating high catalytic turnover numbers in DNA-sequence specific manner. The demonstrated the Dabcyl was designed switch on emission fluorescein dye while switching off rhodamine dye. This setup allows highly sensitive and selective detection DNA-sequences real time.
Reporting live: Triplex formation is used to construct a stem–loop probe, which opened upon binding of the DNA target (red). The triplex molecular beacon composed single strand (blue), stem-forming oligomer (black), and labeled with fluorophore quencher (red blue circles). This concept facilitates introduction further functionalities such as additional quenchers in assembly "superquenched" beacons. Supporting information for this article available on WWW under...
Abstract Bicyclic peptides are promising scaffolds for the development of inhibitors biological targets that proved intractable by typical small molecules. So far, access to bioactive bicyclic peptide architectures is limited due a lack appropriate orthogonal ring-closing reactions. Here, we report chemically olefin (RCM) and alkyne metathesis (RCAM), which enable an efficient chemo- regioselective synthesis complex with variable macrocycle geometries. We also demonstrate formed can be...
Abstract Small GTPases are molecular switches using GDP/GTP alternation to control numerous vital cellular processes. Although aberrant function and regulation of implicated in various human diseases, direct targeting this class proteins has proven difficult, as GTPase signaling is mediated by extensive shallow protein interfaces. Here we report the development inhibitors protein–protein interactions involving Rab proteins, a subfamily GTPases, which key regulators vesicular transport....
Abstract Protein‐Protein‐Interaktionen (PPIs) spielen auf allen Ebenen der Zellorganisation eine wichtige Rolle, was die Entwicklung von PPI‐Inhibitoren äußerst interessant macht. Die Herstellung selektiven Inhibitoren ist wegen relativ flachen und ausgedehnten Protein‐Protein‐Interaktionsflächen oftmals sehr aufwendig. Derartige können beispielsweise durch das Nachahmen Peptidliganden in deren bioaktiver Konformation generiert werden. Für so genannter Peptidmimetika steht Reihe Ansätzen zur...
Structural information about protein-RNA complexes supports the understanding of crucial recognition processes in cell, and it can allow development high affinity ligands to interfere with these processes. In this respect, identification amino acid hotspots is particularly important. contrast protein-protein interactions, silico approaches for interactions lag behind their development. Herein, we report an analysis available structures. We assembled a data set 322 crystal NMR structures...
Small GTPases comprise a family of highly relevant targets in chemical biology and medicinal chemistry research have been considered "undruggable" due to the persisting lack effective synthetic modulators suitable binding pockets. As molecular switches, small control multitude pivotal cellular functions, their dysregulation is associated with many human diseases such as various forms cancer. Rab-GTPases represent largest subfamily are master regulators vesicular transport interacting...
Abstract Nuclear magnetic resonance (NMR) spectroscopy has the intrinsic capabilities to investigate proteins in native environments. In general, however, NMR relies on non‐natural protein purity and concentration increase desired signal over background. We here report efficient specific hyperpolarization of low amounts a target large isotope‐labeled background by combining dynamic nuclear polarization (DNP) selectivity interactions. Using biradical‐labeled ligand, we were able direct...
Protein complexes are defined by the three-dimensional structure of participating binding partners. Knowledge about these structures can facilitate design peptidomimetics which have been applied for example, as inhibitors protein-protein interactions (PPIs). Even though β-sheets participate widely in PPIs, they only rarely served basis peptidomimetic PPI inhibitors, particular when addressing intracellular targets. Here, we present structure-based β-sheet mimetics targeting protein...