- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- bioluminescence and chemiluminescence research
- Protein Degradation and Inhibitors
- Advanced Biosensing Techniques and Applications
- Ubiquitin and proteasome pathways
- Peptidase Inhibition and Analysis
- Receptor Mechanisms and Signaling
University of Bonn
2019-2025
Small-molecule heterobifunctional degraders can effectively control protein levels and are useful research tools.
Intracellular ligands of G protein-coupled receptors (GPCRs) are gaining significant interest in drug discovery. Here, we report the development fluorescent ligand Mz437 (4) targeting CC chemokine receptor CCR7 at an intracellular allosteric site. We demonstrate its experimental power by applying 4 to identify two improved antagonists, SLW131 (10) and SLW132 (21m), developed converting weakly active antagonists into single- or double-digit nanomolar with minimal modifications. The...
Herein, we report the structure-based development of fluorescent ligands targeting intracellular allosteric binding site (IABS) CXC chemokine receptor 2 (CXCR2), a G protein-coupled (GPCR) that has been pursued as drug target in oncology and inflammation. Starting from cocrystallized CXCR2 antagonist 00767013 (1), tetramethylrhodamine (TAMRA)-labeled were designed, synthesized, tested for their suitability reporters to probe IABS CXCR2. By means these studies, developed Mz438 (9a)...
ABSTRACT Intracellularly acting ligands of G protein-coupled receptors (GPCRs) are gaining significant interest in GPCR drug discovery. In this study, we report the development fluorescent ligand Mz437 ( 4 ) targeting CC chemokine receptor CCR7 at an intracellular allosteric site. We demonstrate its experimental power by applying to identify two improved antagonists, SLW131 10 and SLW132 21m ), developed converting weakly active antagonists into single- or double-digit nanomolar with minimal...
Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays fluorescence microscopy. Herein, we report the structure-based development fluorescent ligand targeting intracellular allosteric binding site (IABS) CXC chemokine receptor 2 (CXCR2), class A GPCR that has been pursued as drug target in oncology inflammation. Starting...
Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays fluorescence microscopy. Herein, we report the structure-based development fluorescent ligand targeting intracellular allosteric binding site (IABS) CXC chemokine receptor 2 (CXCR2), class A GPCR that has been pursued as drug target in oncology inflammation. Starting...
Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays fluorescence microscopy. Herein, we report the structure-based development fluorescent ligand targeting intracellular allosteric binding site (IABS) CXC chemokine receptor 2 (CXCR2), class A GPCR that has been pursued as drug target in oncology inflammation. Starting...
Fluorescently labeled ligands are versatile molecular tools to study G protein-coupled receptors (GPCRs) and can be used for a range of different applications, including bioluminescence resonance energy transfer (BRET) assays fluorescence microscopy. Herein, we report the structure-based development fluorescent ligand targeting intracellular allosteric binding site (IABS) CXC chemokine receptor 2 (CXCR2), class A GPCR that has been pursued as drug target in oncology inflammation. Starting...