A5029847792- Antibiotic Resistance in Bacteria
- Alzheimer's disease research and treatments
- Tuberculosis Research and Epidemiology
- Computational Drug Discovery Methods
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Pneumocystis jirovecii pneumonia detection and treatment
- Prion Diseases and Protein Misfolding
- Peptidase Inhibition and Analysis
- Chemical Synthesis and Analysis
- Biofuel production and bioconversion
- Enzyme Production and Characterization
- Receptor Mechanisms and Signaling
- Advanced Proteomics Techniques and Applications
- Multiple Myeloma Research and Treatments
- Bacterial biofilms and quorum sensing
- Lipid Membrane Structure and Behavior
- Click Chemistry and Applications
- Antibiotics Pharmacokinetics and Efficacy
- Neuroscience and Neuropharmacology Research
- Berberine and alkaloids research
- Photochromic and Fluorescence Chemistry
- Microfluidic and Capillary Electrophoresis Applications
- Phagocytosis and Immune Regulation
- Neuropeptides and Animal Physiology
Roche Pharma AG (Germany)
2021-2024
UiT The Arctic University of Norway
2015-2020
Uppsala University
2009-2013
Nofima
2013
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2007
Institute of Molecular Biotechnology
2005
Abstract We report here a recombinant expression system that allows production of large quantities Alzheimer's Aβ(1–40) peptide. The material is competent to dissolve in water solutions with “random‐coil properties,” although its conformation and factual oligomerization state are determined by the physico‐chemical solution conditions. When dissolved 50 mM sodium phosphate buffer (pH 7.4) at 37°C, peptide able undergo nucleated polymerization reaction. aggregation profile characteristically...
Metallo-β-lactamase (MBL) inhibitors can restore the function of carbapenem antibiotics and therefore help to treat infections antibiotic resistant bacteria. In this study, we report novel fragments inhibiting clinically relevant MBL Verona integron-encoded metallo-β-lactamase (VIM-2). The were identified from a library 490 using an orthogonal screening approach based on surface plasmon resonance (SPR) assay combined with enzyme inhibition assay. showed IC50 values between 14 1500 μM ligand...
Abstract The formation of polypeptide aggregates represents a nucleated polymerization reaction in which an initial nucleation event (lag phase) is followed by the extension newly formed nuclei into larger aggregates, including fibrils (growth phase). efficiencies these reactions relate to lag time and rate aggregation phase), can be determined from experimental curves. Here we present mutagenic analysis replace valine 18 Alzheimer's Aβ (1–40) peptide with 17 different amino acids determine...
BACE-1 is one of the aspartic proteases involved in cleavage β amyloid peptide, an initial step formation plaques whose toxicity induces neuron death Alzheimer's disease patients. One central issues search novel inhibitors optimum pH for binding to enzyme. It known that enzyme has optimal catalytic activity at acidic pH, while cell active may bind optimally higher pH. In this work we determine effect on affinities a set inhibitors, with variety chemical motifs, ectodomain region by surface...
Abstract Removal of apoptotic cells by phagocytes (also called efferocytosis) is a crucial process for tissue homeostasis. Professional express plethora surface receptors enabling them to sense and engulf cells, thus avoiding persistence dead cellular debris their consequent effects. Dysregulation efferocytosis thought lead secondary necrosis associated inflammation immune activation. Efferocytosis in primarily murine macrophages dendritic has been shown require TAM RTKs, with MERTK AXL...
Increasing evidence indicates that polypeptide aggregation often involves a nucleation and growth phase, although the relationship between factors determine these two phases has not yet been fully clarified. We present here an analysis of several mutations at different sites Abeta(1-40) peptide, including those associated with early onset forms Alzheimer's disease, which reveals effects specific amino acid substitutions in sequence this peptide are strongly modulated by their structural...
The increasing number of pathogens expressing metallo-β-lactamases (MBLs), and in this way achieving resistance to β-lactam antibiotics, is a significant threat global public health. A promising strategy treat such resistant the co-administration MBL inhibitors together with antibiotics. However, an inhibitor suitable for clinical use has not yet been identified. Verona integron-encoded metallo-β-lactamase 2 (VIM-2) widespread broad substrate spectrum hence interesting drug target treatment...
Enzymatic depolymerization of recalcitrant polysaccharides plays a key role in accessing the renewable energy stored within lignocellulosic biomass, and natural biodiversities may be explored to discover microbial enzymes that have evolved conquer this task various environments. Here, metagenome from thermophilic community was mined yield novel, thermostable cellulase, named mgCel6A, with activity on an industrial cellulosic substrate (sulfite-pulped Norway spruce) glucomannanase side...
The spread of antibiotic resistant bacteria is a global threat that shakes the foundations modern healthcare. β-Lactamases are enzymes confer resistance to β-lactam antibiotics in bacteria, and there critical need for new inhibitors these combination therapy together with an antibiotic. With this mind, we have screened library 490 fragments identify starting points development class D β-lactamase oxacillinase-48 (OXA-48) through surface plasmon resonance (SPR), dose-rate inhibition assays,...
Monoclonal antibody (mAb) pharmaceuticals consist of a plethora different proteoforms with functional characteristics, including pharmacokinetics and pharmacodynamics, requiring their individual assessment. Current binding techniques do not distinguish between coexisting tedious production enriched proteoforms. Here, we have developed an approach based on mobility shift-affinity capillary electrophoresis–mass spectrometry (ACE–MS), which permitted us to determine the mAb Fc receptors (FcRs)....
We have determined the critical concentrations of a set 18 variants Alzheimer's Abeta(1-40) peptide, each carrying different residue at position 18. find that depend on hydrophobicity and beta-sheet propensity 18, therefore properties we identified previously to affect also kinetics by which these peptides aggregate. Since can be related Gibbs free energy aggregation (DeltaG), data imply link between thermodynamics in sequences form very stable aggregates are those such rapidly.
High-affinity binders for the C-reactive protein (CRP), with dissociation constants in pM to nM range and selectivities human serum comparable those of antibodies, were obtained by conjugation 16 designed polypeptides phosphocholine, a small molecule that binds CRP KD value 5 μM (see picture). The not specifically recognize bind an adapted fit mechanism. Detailed facts importance specialist readers are published as ”Supporting Information”. Such documents peer-reviewed, but copy-edited or...
Many class D β-lactamases form dimers in solution. The functional basis of the dimerization OXA-48-like is not known, but order to understand structural requirements for OXA-48, we have characterized dimer interface. Size exclusion chromatography, small angle X-ray scattering (SAXS), and nuclear magnetic resonance (NMR) were used confirm oligomeric state OXA-48 crystallographic structures elucidate key interactions dimerization. In silico residue scanning combined with site-directed...
Metallo-β-lactamases (MBLs) are an emerging cause of bacterial antibiotic resistance by hydrolysing all classes β-lactams except monobactams, and the MBLs not inhibited clinically available serine-β-lactamase inhibitors. Two most commonly encountered in clinical isolates worldwide – New Delhi metallo-β-lactamase (NDM-1) Verona integron-encoded (VIM-2) included this study. A series several NH-1,2,3-triazoles was prepared a three-step protocol utilizing Banert cascade reaction as key step. The...
Abstract Amyloid formation is a nucleation‐dependent process that accelerated dramatically in vivo and vitro upon addition of appropriate fibril seeds. A potent species barrier can be effective this reaction if donor recipient come from different biological species. This thought to reflect differences the amino acid sequence between seed target polypeptide. Here we present an mutagenic cross‐seeding analysis Alzheimer's Aβ(1‐40) peptide which mapped out effect systematically varied...
The screening of extracts from marine organisms is a widely used strategy to discover new drug leads. A common problem in the process generation false positive hits through unspecific effects complex chemical composition crude extracts. In this study, we explored combination fluorescence resonance energy transfer (FRET) based activity assay and surface plasmon (SPR) binding avoid problem. An aqueous extract was prepared rest raw material Norwegian spring spawning herring, further...