A5103069605- Chemical Synthesis and Analysis
- Click Chemistry and Applications
- HER2/EGFR in Cancer Research
- Synthesis and biological activity
- Microbial Natural Products and Biosynthesis
- Peptidase Inhibition and Analysis
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Fullerene Chemistry and Applications
- Synthesis and Properties of Aromatic Compounds
- Synthesis and Characterization of Heterocyclic Compounds
- Machine Learning in Bioinformatics
- Liquid Crystal Research Advancements
- Cell Adhesion Molecules Research
- Synthesis and Reactions of Organic Compounds
- Antimicrobial Peptides and Activities
- Enzyme Structure and Function
- Microbial Metabolites in Food Biotechnology
- Cancer Treatment and Pharmacology
- Advanced Breast Cancer Therapies
- Redox biology and oxidative stress
- Metal complexes synthesis and properties
- Synthesis of heterocyclic compounds
- Crystal structures of chemical compounds
ETH Zurich
2022-2024
Board of the Swiss Federal Institutes of Technology
2023-2024
Czech Academy of Sciences, Institute of Microbiology
2022
Pfizer (United States)
2007-2016
Max Planck Institute for Polymer Research
2002
University of Potsdam
2002
First generation EGFR TKIs (gefitinib, erlotinib) provide significant clinical benefit for NSCLC cancer patients with oncogenic mutations. Ultimately, these patients' disease progresses, often driven by a second-site mutation in the kinase domain (T790M). Another liability of first drugs is severe adverse events inhibition WT EGFR. As such, our goal was to develop highly potent irreversible inhibitor largest selectivity ratio between drug-resistant double mutants (L858R/T790M, Del/T790M) and...
Abstract The tetrazine ligation is an inverse electron-demand Diels–Alder reaction widely used for bioorthogonal modifications due to its versatility, site specificity and fast kinetics. A major limitation has been the incorporation of dienophiles in biomolecules organisms, which relies on externally added reagents. Available methods require tetrazine-reactive groups by enzyme-mediated ligations or unnatural amino acid incorporation. Here we report a strategy, termed TyrEx (tyramine...
Liquid-crystalline polyfluorene (PF) homopolymers substituted with chiral alkyl side chains were synthesized, and their chiroptical properties in the solid state investigated by means of circular dichroism (CD), circularly polarized photoluminescence (CPPL), electroluminescence (CPEL) measurements. Polarization-selective scattering light is shown to cause artifacts absorption emission spectra wavelength range near or above edge, a measurement scheme avoid these presented. For all...
Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge enzymology. Ribosomally synthesized post-translationally modified peptides (RiPPs) are a rapidly growing class of products featuring diverse non-canonical amino acids introduced by maturation enzymes as class-defining characteristic. Underexplored RiPP sources, such the human microbiome, oceans, uncultured microorganisms, plants rich hunting grounds for novel Unusual α- β-amino acids,...
Ribosomally synthesized and post-translationally modified peptides (RiPPs) are natural products that feature diverse modifications. They show a wide range of biological activities therefore great interest for drug discovery protein engineering. An unusual modification found in spliceotide RiPPs is the installation β-amino acid residues with side chains, generated by backbone excision tyramine moiety derived from tyrosine. We have previously shown can be adapted to engineering greatly expand...
Abstract Radical S ‐adenosyl methionine enzymes catalyze a diverse repertoire of post‐translational modifications in protein and peptide substrates. Among these, an exceptional mechanistically obscure example is the installation α‐keto‐β‐amino acid residues by formal excision tyrosine‐derived tyramine unit. The responsible spliceases are key maturases widespread family natural products termed spliceotides that comprise potent protease inhibitors, with installed β‐residues being crucial for...
Abstract Focal adhesion kinase (FAK) is a non-tyrosine that localizes to focal plaques. It activated in response intergin binding cellular ligands and when phosphorylated inhibits anoikis allowing for anchorage independent cell growth. Recent studies have shown increased FAK expression phosphorylation status many types of invasive aggressive human tumors strongly suggesting possible target anticancer chemotherapy. Literature, house HTS de novo identified 2, 4-diaminopyrimidines as potent...
Abstract Radical S ‐adenosyl methionine enzymes catalyze a diverse repertoire of post‐translational modifications in protein and peptide substrates. Among these, an exceptional mechanistically obscure example is the installation α‐keto‐β‐amino acid residues by formal excision tyrosine‐derived tyramine unit. The responsible spliceases are key maturases widespread family natural products termed spliceotides that comprise potent protease inhibitors, with installed β‐residues being crucial for...
The reaction of (E)-tert-butyl 4-[3-(dimethyl-amino)acrylo-yl]piperidine-1-carboxyl-ate with methyl-hydrazine leads to the formation title compound, C(14)H(23)N(3)O(2), a 1-methyl-1H-pyrazol-5-yl substituent. plane pyrazole ring forms dihedral angle 33.4 (1)° approximate mirror piperidine ring.
The title compound, C(12)H(13)ClN(6), was prepared by reaction of 4,5-dichloro-7H-pyrrolo[2,3-d]pyrimidine with 2-(1H-imid-azol-4-yl)-N-methyl-ethanamine, and the X-ray study confirmed that chloro-substituent in six-membered ring replaced reaction. exocyclic N atom environment is approximately coplanar pyrrolo[2,3-d]pyrimidine [corresponding dihedral angle 5.5 (1)°], whereas mean plane N-C-C-C link connecting imidazolyl almost exactly orthogonal to bicyclic system [dihedral = 91.6 (2)°]....
March, 2012; based on sample preparation guide v2, catalog # RS-930-1021, part 15026495 Rev. A, August 2011 Modifications: samples in PCR tubes (because a plate/seal will not be used, some numbered steps are skipped); include two rounds of poly-A selection (with separate sets beads); repeat clean-up step after to remove additional adapters; elute with 1.5 ul less volume off beads (to leave 1 behind, 2.5 ul)
β-Amino residues are regarded as extremely rare features among ribosomal products. They can be installed by a remarkable non-canonical enzymatic splicing process occurring in some Nif11-type ribosomally synthesized and post-translationally modified peptide (RiPP) pathways from select cyanobacteria. The functions of the final pathway products remained unknown. Here, global bioinformatic analysis suggested an unexpectedly broad distribution β-amino acid diverse bacterial lineages well archaea....
Abstract Die aus den Benzaldehyden (I) durch Umsetzung mit Anilinen (II) und Kaliumcyanid hergestellten AryI‐arylaminoacetonitriIe (III) werden " Permanganat zu Aryliminoderivaten (IV) dehydriert.