A5106127064- Antimicrobial Peptides and Activities
- Biochemical and Structural Characterization
- Microbial Natural Products and Biosynthesis
- Gastrointestinal Tumor Research and Treatment
- Neuroscience and Neuropharmacology Research
- Peptidase Inhibition and Analysis
- Trypanosoma species research and implications
- Pharmacological Receptor Mechanisms and Effects
- Receptor Mechanisms and Signaling
- Research on Leishmaniasis Studies
- Glaucoma and retinal disorders
- Corneal surgery and disorders
- Studies on Chitinases and Chitosanases
- Microbial Metabolic Engineering and Bioproduction
- Dermatology and Skin Diseases
- Bioinformatics and Genomic Networks
- Advancements in Transdermal Drug Delivery
- Coccidia and coccidiosis research
- Invertebrate Immune Response Mechanisms
- Venomous Animal Envenomation and Studies
- Protein Hydrolysis and Bioactive Peptides
- Corneal Surgery and Treatments
- Cardiac tumors and thrombi
- Click Chemistry and Applications
- Plant biochemistry and biosynthesis
Technische Universität Berlin
2018-2025
University of Southern California
2025
TU Dortmund University
2020-2023
Johannes Gutenberg University Mainz
2016-2022
Knappschaftsklinikum Saar
2020
Czech Academy of Sciences, Institute of Biotechnology
2019
Kiel University
2007-2016
Charité - Universitätsmedizin Berlin
2009-2016
Abstract Nucleotide-binding oligomerization domain-like receptors (NLRs) are a group of intracellular proteins that mediate recognition pathogen-associated molecular patterns or other cytosolic danger signals. Mutations in NLR genes have been linked to variety inflammatory diseases, underscoring their pivotal role host defense and immunity. This report describes the genomic organization regulation human family member NLRC5 aspects cellular function encoded protein. We analyzed...
Hydramacin-1 is a novel antimicrobial protein recently discovered during investigations of the epithelial defense ancient metazoan Hydra. The amino acid sequence hydramacin-1 shows no homology to any known proteins. Determination solution structure revealed that possesses disulfide bridge-stabilized alphabeta motif. This motif common scaffold knottin fold. structurally closest relatives are scorpion oxin-like superfamily. Within this superfamily establishes new family proteins all share...
A disintegrin and metalloprotease-17 (ADAM17) is a major sheddase responsible for the regulation of wide range biological processes, like cellular differentiation, regeneration, or cancer progression. Hitherto, mechanism regulating enzymatic activity ADAM17 poorly understood. Recently, protein-disulfide isomerase (PDI) was shown to interact with down-regulate its activity. Here we demonstrate by NMR spectroscopy tandem-mass spectrometry that PDI directly interacts membrane-proximal domain...
We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from known inhibitor, in first and second steps appropriate substituents warhead are selected on basis quantum mechanical (QM) computations hybrid approaches combining QM with molecular mechanics (QM/MM). In third step recognition unit is optimized using docking noncovalent complex. These predictions finally verified by QM/MM or dynamic simulations. The applicability our approach...
The unexpected resistance of psoriasis lesions to fungal infections suggests local production an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional scale extracts and identified the Cys-reduced form S100A7/psoriasin (redS100A7) as a principal redS100A7 inhibits various filamentous fungi, including mold Aspergillus fumigatus, but not Candida albicans. Antifungal was inhibited by Zn(2+), suggesting that interferes with zinc homeostasis. Because S100A7-mutants...
For at least two decades, nanoparticles have been investigated for their capability to deliver topically applied substances through the skin barrier. Based on findings that are highly suitable penetrating blood–brain barrier, use drug delivery has become a topic of intense research. In spite research efforts by academia and industry, commercial product permitting nanoparticle-assisted drugs not yet developed. However, approximately 600 nm in diameter shown penetrate efficiently into hair...
The emblematic hydrothermal worm Alvinella pompejana is one of the most thermo tolerant animal known on Earth. It relies a symbiotic association offering unique opportunity to discover biochemical adaptations that allow animals thrive in such hostile habitat. Here, by studying Pompeii worm, we report discovery first antibiotic peptide from deep-sea organism, namely alvinellacin. After purification and sequencing, both gene tertiary structures were elucidated. As epibionts are not cultivated...
Dipeptidyl nitroalkenes are potent reversible inhibitors of cysteine proteases. Inhibitor 11 resulted to be the most one with Ki values 0.49 and 0.44 nM against rhodesain cruzain, respectively. According enzymatic dilution dialysis experiments, as well computational NMR studies, dipeptidyl tightly binding covalent inhibitors.
Abstract We present a Penicillium rubens strain with an industrial background in which the four highly expressed biosynthetic gene clusters (BGC) required to produce penicillin, roquefortine, chrysogine and fungisporin were removed. This resulted minimal secondary metabolite background. Amino acid pools under steady-state growth conditions showed reduced levels of methionine increased intracellular aromatic amino acids. Expression profiling remaining BGC core genes untargeted mass...
The mitochondrial DNA (mtDNA) can trigger immune responses and directly entrap pathogens, but it is not known to encode for active factors. system traditionally thought be exclusively nuclear-encoded. Here, we report the identification of a mitochondrial-encoded host defense peptide (HDP) that presumably derives from primordial proto-mitochondrial bacteria. We demonstrate MOTS-c (mitochondrial open reading frame twelve S rRNA type-c) amphipathic cationic with direct antibacterial...
Antifungal peptides are promising drug candidates to fight fungal infections in the clinics and agriculture. However, recent data suggest that antifungal might also play a role within their own producing organism survive nutrient limiting conditions. We have therefore studied function of AnAFP Aspergillus niger more detail. To achieve this, we established Tet-on controlled anafp expression system, which allowed us study null an overexpression phenotype same isolate. observed increased...
Abstract Background Fungal-based composites have emerged as renewable, high-performance biomaterials that are produced on lignocellulosic residual streams from forestry and agriculture. Production at an industrial scale promises to revolutionize the world humans inhabit by generating sustainable, low emission, non-toxic biodegradable construction, packaging, textile, other materials. The polypore Fomes fomentarius is one of basidiomycete species used for biomaterial production, yet nothing...
Understanding the genetic, molecular and evolutionary basis of cysteine-stabilized antifungal proteins (AFPs) from fungi is important for understanding whether their function mainly defensive or associated with fungal growth development. In current study, a transcriptome meta-analysis Aspergillus niger γ-core protein AnAFP was performed to explore co-expressed genes pathways, based on independent expression profiling microarrays covering 155 distinct cultivation conditions. This analysis...
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, pathogen causing Human African Trypanosomiasis, and validated drug target. Recently, we reported the development α-halovinylsulfones as new class covalent reversible inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, most potent selective inhibitor in series, shows single-digit nanomolar affinity high selectivity toward mammalian cathepsins B L....
Methyl groups can have profound effects in drug discovery but the underlying mechanisms are diverse and incompletely understood. Here we report stereospecific effect of a single, solvent-exposed methyl group bicyclic [4.3.1] aza-amides, robustly leading to 2 10-fold increase binding affinity for FK506-binding proteins (FKBPs). This resulted most potent efficient FKBP ligands known date. By combination co-crystal structures, isothermal titration calorimetry (ITC), density-functional theory...
To achieve climate neutrality, fundamentally new concepts of circularity need to be implemented by the building sector as it contributes 40% anthropogenic CO2 emission. Fungal biotechnology can make a significant contribution here and help eliminate fossil dependency for material production. Recently, we have shown that medicinal polypore Fomes fomentarius feeds well on renewable lignocellulosic biomass produces composite materials could potentially replace fuel-based expanded polystyrene...
Despite partial sequence identity and structural similarity, human β-defensin 3 (HBD3) kills Staphylococcus aureus with a 4- to 8-fold higher efficiency than 2 (HBD2), whereas the activities against Escherichia coli are identical. The design characterization of HBD2/HBD3 chimeric peptides revealed that distinct molecular regions responsible for their divergent killing properties. Two chimeras killed both E. S. an even efficacy wild-type molecules. Moreover, one these two maintained its high...