A5081694672- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- HER2/EGFR in Cancer Research
- Peptidase Inhibition and Analysis
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Catalytic Reactions
- Advanced biosensing and bioanalysis techniques
- Biochemical and Structural Characterization
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Biochemical and Molecular Research
- Advanced Proteomics Techniques and Applications
- Cell Adhesion Molecules Research
- Microbial Natural Products and Biosynthesis
- Mass Spectrometry Techniques and Applications
- Virus-based gene therapy research
- Influenza Virus Research Studies
- Protein Structure and Dynamics
- Bacteriophages and microbial interactions
- Cancer Treatment and Pharmacology
- Biotin and Related Studies
- Antimicrobial Peptides and Activities
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2016-2025
Humboldt-Universität zu Berlin
2016-2025
Forschungsverbund Berlin
2017-2025
Florida State University
2023
Ludwig-Maximilians-Universität München
2015-2023
The University of Queensland
2023
Durham University
2023
Shanghai Institute of Organic Chemistry
2023
ETH Zurich
2023
University of Manchester
2023
Abstract The delivery of free molecules into the cytoplasm and nucleus by using arginine‐rich cell‐penetrating peptides (CPPs) has been limited to small cargoes, while large cargoes such as proteins are taken up trapped in endocytic vesicles. Based on recent work, which we showed that transduction efficiency CPPs can be greatly enhanced cyclization, aim was use cyclic transport full‐length proteins, this study green fluorescent protein (GFP), cytosol living cells. Cyclic linear CPP–GFP...
Abstract Die Untersuchung biologischer Fragestellungen mit chemischen Methoden wird meist als “Chemische Biologie” bezeichnet und setzt voraus, dass biologisch relevante Makromoleküle, wie Peptide Proteine, chemisch zugänglich sind. Auf der Festphasensynthese von Peptiden aufbauend wurden viele chemoselektive Ligations‐ Modifikationstechniken zur Verknüpfung synthetischer oder funktionaler Einheiten zu größeren synthetischen, relevanten Makromolekülen entwickelt. Dieser Aufsatz fasst die...
Extending the toolbox: The title reaction was identified as a chemoselective means to modify azides in peptides and proteins high yields at room temperature various solvents including aqueous buffers physiological pH. In combination with nonnatural protein translation Staudinger-phosphite allows site-specific incorporation of phosphorylated Tyr analogues proteins.
Phosphorylation of the microtubule-associated Tau protein plays a major role in regulation its activity tubulin polymerization and/or stabilization microtubule assembly. A dysregulation phosphorylation/dephosphorylation balance leading to hyperphosphorylation proteins neurons is thought favor their aggregation into insoluble filaments. This turn might underlie neuronal death as encountered many neurodegenerative disorders, including Alzheimer's disease. Another post-translational...
The attachment of linear polyethylene glycol (PEG) to peptides and proteins for their stabilization in vivo applications is a milestone pharmaceutical research protein-drug development. However, conventional methods often lead heterogeneous PEGylation mixtures with reduced protein activity. Current synthetic efforts aim provide site-specific approaches by chemoselective targeting canonical noncanonical amino acids improve the PEG architecture. This synopsis highlights recent work this area,...
Abstract To inhibit binding of the influenza A virus to host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles with nanomolar affinity via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a presentation. We could demonstrate in vitro that by increasing size polymer scaffold adjusting peptide density, viral infection is drastically reduced. Such conjugate qualified also an vivo scenario. With this...
Abstract A novel chemoenzymatic approach for simple and fast site‐specific protein labeling is reported. Recombinant tubulin tyrosine ligase (TTL) was repurposed to attach various unnatural derivatives as small bioorthogonal handles proteins containing a short tubulin‐derived recognition sequence (Tub‐tag). This strategy enables broad range of high‐yielding chemoselective C‐terminal modifications on isolated or in cell lysates applications biochemistry, biology, beyond, demonstrated by the...
Abstract We describe a new technique in protein synthesis that extends the existing repertoire of methods for modification: A chemoselective reaction induces reactivity subsequent bioconjugation. An azide‐modified building block reacts first with an ethynylphosphonite through Staudinger‐phosphonite (SPhR) to give ethynylphosphonamidate. The resulting electron‐deficient triple bond subsequently undergoes cysteine‐selective proteins or antibodies. demonstrate ethynylphosphonamidates display...
The delivery of entire functional proteins into living cells is a long-sought goal in science. Cyclic cell-penetrating peptides (cCPPs) have proven themselves to be potent vehicles carry upon conjugation the cytosol with immediate bioavailability via non-endosomal uptake pathway. With this strategy, we pursue cytosolic mCherry, medium-sized fluorescent protein. Afterward, achieve subcellular mCherry different intracellular loci by genetic fusion targeting protein sequence. We show efficient...
Two birds with one stone! An intramolecular traceless Staudinger ligation was employed to synthesize cyclic peptides. The final amide bond formation induced by deprotection of the azidopeptide phosphinothioesters. Treatment trifluoroacetic acid (TFA) results in simultaneous removal borane along protecting groups on peptide side chains, and chemoselective cyclization ensues. Supporting information for this article is available WWW under...
Abstract The targeting of metabolically labeled glycans with conventional MRI contrast agents has proved elusive. In this work, which further expands the utility xenon Hyper‐CEST biosensors in cell experiments, we present first successful molecular imaging such using MRI. Xenon are a novel class very high sensitivity. We designed multimodal biosensor for both fluorescent and detection that is targeted to sialic acid through bioorthogonal chemistry. Through use state art live‐cell bioreactor,...
Protein phosphorylation controls major processes in cells. Although of serine, threonine, and tyrosine also recently histidine arginine are well-established, the extent biological significance lysine has remained elusive. Research this area been particularly limited by inaccessibility peptides proteins that phosphorylated at specific residues, which incompatible with solid-phase peptide synthesis (SPPS) due to intrinsic acid lability P(═O)–N phosphoramidate bond. To address issue, we have...
In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity a following thiol addition. We show that by varying phosphonamidate ester substituent can fine-tune addition even control functional properties final...
Abstract Requirements for novel bioconjugation reactions the synthesis of antibody–drug conjugates (ADCs) are exceptionally high, since conjugation selectivity as well stability and hydrophobicity linkers payloads drastically influence performance safety profile final product. We report Cys‐selective ethynylphosphonamidates new reagents rapid generation efficacious ADCs from native non‐engineered monoclonal antibodies through a simple one‐pot reduction alkylation. Ethynylphosphonamidates can...
Diethynyl phosphinates were developed as bisfunctional electrophiles for the site-selective modification of peptides, proteins and antibodies. One their electron-deficient triple bonds reacts selectively with a thiol positions an electrophilic moiety subsequent intra- or intermolecular reaction another thiol. The obtained conjugates found to be stable in human plasma presence small thiols. We further demonstrate that this method is suitable generation functional protein intracellular...
Phosphorylation of the neuronal microtubule-associated Tau protein plays a critical role in aggregation process leading to formation insoluble intraneuronal fibrils within Alzheimer’s disease (AD) brains. In recent years, other posttranslational modifications (PTMs) have been highlighted regulation (dys)functions. Among these PTMs, O -β-linked N-acetylglucosaminylation ( -GlcNAcylation) modulates phosphorylation and aggregation. We here focus on PHF-1 phospho-epitope C-terminal domain that...