A5010222484- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- Chromatin Remodeling and Cancer
- Protein Degradation and Inhibitors
- Pneumocystis jirovecii pneumonia detection and treatment
- Marine Sponges and Natural Products
- Computational Drug Discovery Methods
- Asymmetric Hydrogenation and Catalysis
- Multiple Myeloma Research and Treatments
- Photoreceptor and optogenetics research
- Plant biochemistry and biosynthesis
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Cancer Mechanisms and Therapy
- Peptidase Inhibition and Analysis
- X-ray Diffraction in Crystallography
- Glycosylation and Glycoproteins Research
- Photochromic and Fluorescence Chemistry
- Advanced biosensing and bioanalysis techniques
- Crystallization and Solubility Studies
- Cell Image Analysis Techniques
- Synthetic Organic Chemistry Methods
- Ubiquitin and proteasome pathways
- Monoclonal and Polyclonal Antibodies Research
- Tuberculosis Research and Epidemiology
Novartis (Switzerland)
2024-2025
Max Planck Institute of Molecular Physiology
2020-2024
Oxford Research Group
2015
University of Oxford
2015
University of Zurich
2013
Activating mutations in the rat sarcoma (RAS) genes HRAS, NRAS and KRAS collectively represent most frequent oncogenic driver human cancer1. They have previously been considered undruggable, but advances past few years led to clinical development of agents that target KRAS(G12C) KRAS(G12D) mutants, yielding promises therapeutic responses at tolerated doses2. However, selectively NRAS(Q61*) mutants (* represents 'any'), second-most-frequent melanoma, are still lacking. Here we identify SHOC2,...
Interleukin-36 receptor (IL-36R), belonging to the IL-1 family, is crucial for host defense and tissue repair. Targeting cytokine receptors with low molecular weight (LMW) compounds remains challenging due their interaction large surface area of cytokine. In this study, two encoded library technologies are used identify LMW molecules binding IL-36R's extracellular domain. The mRNA-based display technique identifies 36R-P138, a macrocyclic peptide blocking IL-36R signaling. Importantly, its...
Abstract P‐Amidites can be used in iterative couplings to selectively give mixed P III –P V anhydrides. These intermediates oxidized followed by a rapid removal of the two terminal fluorenylmethyl groups. An synthesis (coupling, oxidation, deprotection) nucleoside oligophosphates carried out solution and on solid support. The coupling rates yields are high, procedures convenient (non‐dry reagents solvents, ambient conditions, unprotected nucleotides), purification is very simple. method...
Abstract Natural product (NP) structures are a rich source of inspiration for the discovery new biologically relevant chemical matter. In natural inspired pseudo‐NPs, NP‐derived fragments combined de novo in unprecedented arrangements. Described here is design and synthesis 155‐member pyrroquinoline pseudo‐NP collection which characteristic tetrahydroquinoline pyrrolidine NP classes with eight different connectivities regioisomeric Cheminformatic analysis biological evaluation compound by...
Abstract Phosphoanhydrides (P‐anhydrides) are ubiquitously occurring modifications in nature. Nucleotides and their conjugates, for example, among the most important building blocks signaling molecules cell biology. To study manipulate biological functions, a diverse range of analogues have been developed. Phosphate‐modified successfully applied to proteins that depend on these abundant cellular blocks, but very often both preparation purification challenging. This discloses general access...
Abstract P‐Amidite können verwendet werden, um in einer iterativen Kupplung selektiv gemischte P III ‐P V ‐Anhydride herzustellen. Diese Intermediate oxidiert und die terminalen Fluorenylmethylgruppen darauffolgend abgespalten werden. Eine iterative Synthese (Kupplung, Oxidation, Entschützung) von Nukleosidoligophosphaten kann sowohl Lösung als auch auf festen Phase durchgeführt Die Geschwindigkeiten Ausbeuten der einzelnen Schritte sind hoch, das Vorgehen einfach (keine wasserfreien...
The ARID1A and ARID1B subunits are mutually exclusive components of the BAF variant SWI/SNF chromatin remodeling complexes. Loss function mutations in frequently observed various cancers, resulting a dependency on paralog for cancer cell proliferation. However, has never been targeted directly, high degree sequence similarity to poses challenge development selective binders. In this study, we used mRNA display identify peptidic ligands that bind with nanomolar affinities showed selectivity...
Abstract Natural product (NP) structures are a rich source of inspiration for the discovery new biologically relevant chemical matter. In natural inspired pseudo‐NPs, NP‐derived fragments combined de novo in unprecedented arrangements. Described here is design and synthesis 155‐member pyrroquinoline pseudo‐NP collection which characteristic tetrahydroquinoline pyrrolidine NP classes with eight different connectivities regioisomeric Cheminformatic analysis biological evaluation compound by...
Abstract Phenotypic assays detect small‐molecule bioactivity at functionally relevant cellular sites, and inherently cover a variety of targets mechanisms action. They can uncover new small molecule‐target pairs may give rise to novel biological insights. By means an osteoblast differentiation assay which employs Hedgehog (Hh) signaling agonist as stimulus monitors endogenous marker for osteoblasts, we identified pyrrolo[3,4‐ g ]quinoline (PQ) pseudo‐natural product (PNP) class osteogenesis...
Abstract Phenotypic assays detect small‐molecule bioactivity at functionally relevant cellular sites, and inherently cover a variety of targets mechanisms action. They can uncover new small molecule‐target pairs may give rise to novel biological insights. By means an osteoblast differentiation assay which employs Hedgehog (Hh) signaling agonist as stimulus monitors endogenous marker for osteoblasts, we identified pyrrolo[3,4‐ g ]quinoline (PQ) pseudo‐natural product (PNP) class osteogenesis...