A5040229188- Dendrimers and Hyperbranched Polymers
- Chemical Synthesis and Analysis
- RNA Interference and Gene Delivery
- Antimicrobial Peptides and Activities
- Glycosylation and Glycoproteins Research
- Porphyrin Metabolism and Disorders
- Advanced biosensing and bioanalysis techniques
- Folate and B Vitamins Research
- Bacteriophages and microbial interactions
- Carbohydrate Chemistry and Synthesis
- Biochemical and Structural Characterization
- Click Chemistry and Applications
- Porphyrin and Phthalocyanine Chemistry
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Asymmetric Synthesis and Catalysis
- Enzyme Structure and Function
- Protein Structure and Dynamics
- Bacterial Genetics and Biotechnology
- Computational Drug Discovery Methods
- DNA and Nucleic Acid Chemistry
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Synthetic Organic Chemistry Methods
- CRISPR and Genetic Engineering
University of Bern
2014-2024
Université Joseph Fourier
2007
Centre National de la Recherche Scientifique
2007
Board of the Swiss Federal Institutes of Technology
1984
The dendritic architecture applied to peptides provides a practical entry into globular macromolecules resembling proteins. A modular design was chosen using divergent synthesis on solid support alternating proteinogenic α-amino acids with branching diamino acids, producing peptide dendrimers molecular weight of 3−5 kDa. Initial studies focused models for hydrolases and produced esterase featuring histidine as the key catalytic residue. Variations amino acid composition led enantioselective...
Zn complexes of proline, lysine and arginine are efficient catalysts for the aldol addition p-nitrobenzaldehyde acetone in aqueous medium, giving quantitative yields enantiomeric excesses up to 56% with 5 mol% at room temperature.
Inhibiting factors: Biofilm inhibition is achieved with a phenylgalactosyl peptide dendrimer (see picture) that binds to the galactose-specific lectin LecA of P. aeruginosa. The multivalency ligands critical for biofilm inhibition, although nature linker between and galactose can provide additional contacts also has an effect on interaction. spread antibiotic resistant bacteria one most pressing problems in human health today.1 In case opportunistic pathogen Pseudomonas aeruginosa, which...
Multidrug-resistant opportunistic bacteria, such as Pseudomonas aeruginosa, represent a major public health threat. Antimicrobial peptides (AMPs) and related peptidomimetic systems offer an attractive opportunity to control these pathogens. AMP dendrimers (AMPDs) with high activity against multidrug-resistant clinical isolates of P. aeruginosa Acinetobacter baumannii were now identified by systematic survey the peptide sequences within branches distinct type third-generation dendrimers....
New antibiotics are urgently needed to address multidrug-resistant (MDR) bacteria. Herein we report that second-generation (G2) peptide dendrimers bearing a fatty acid chain at the dendrimer core efficiently kill Gram-negative bacteria including Pseudomonas aeruginosa and Acinetobacter baumannii, two of most problematic MDR worldwide. Our active TNS18 is also against Gram-positive methicillin-resistant Staphylococcus aureus. Based on circular dichroism molecular dynamics studies, hypothesize...
Glycopeptide dendrimers targeting <italic>P. aeruginosa</italic> lectins yielded to crystallography and acted in synergy with tobramycin for biofilm inhibition dispersal.
The contribution of the dendritic structure in catalysis ester hydrolysis was investigated with a systematic peptide dendrimer series increasing generation number (G1-G4) containing catalytic consensus sequence His-Ser all branches. A strong positive effect observed up to 100-fold increased histidine reactivity between G1 and G4. Kinetic studies isothermal calorimetric titration experiments showed that resulted from cooperativity binding catalysis.
The galactose specific lectin LecA mediates biofilm formation in the opportunistic pathogen P. aeruginosa . interaction between and aromatic β-galactoside inhibitors involves an intermolecular CH-π T-shape C(ε1)-H of residue His50 ring galactoside aglycone. generality this was tested a diverse family β-galactosides. binding to β-galactosides (KD ∼ 8 μM) consistently stronger than aliphatic 36 μM). observed X-ray crystal structures six different complexes, with shorter van der Waals distances...
Efficient DNA delivery into cells is the prerequisite of genetic manipulation organisms in molecular and cellular biology as well as, ultimately, nonviral gene therapy. Current reagents, however, are relatively inefficient, structure–activity relationships to guide their improvement hard come by. We now explore peptide dendrimers a new type transfection reagent provide quantitative framework for evaluation. A collection with cationic hydrophobic amino acid motifs (such KK, KA, KH, KL, LL)...
N-Linked glycosylation is an essential post-translational protein modification in the eukaryotic cell. The initial transfer of oligosaccharide from a lipid carrier onto asparagine residues within consensus sequon catalyzed by oligosaccharyltransferase (OST). first X-ray structure complete bacterial OST enzyme, Campylobacter lari PglB, was recently determined. To understand mechanism we have quantified binding and turnover vitro using purified enzyme fluorescently labeled, synthetic peptide...
ABSTRACT The in vitro activity of the novel antimicrobial peptide dendrimer G3KL was evaluated against 32 Acinetobacter baumannii (including 10 OXA-23, 7 OXA-24, and 11 OXA-58 carbapenemase producers) 35 Pseudomonas aeruginosa 18 VIM 3 IMP strains compared to activities standard antibiotics. Overall, both species collections showed MIC 50/90 values 8/8 μg/ml minimum bactericidal concentrations at which 50% or 90% tested are killed (MBC ) μg/ml. is a promising molecule with antibacterial...
We recently discovered that peptide dendrimers such as G3KL ((KL)8(KKL)4(KKL)2KKL, K = branching l-lysine) exert strong activity against Gram-negative bacteria including Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Herein, we report a detailed mechanistic study using fluorescence labeled analogs bearing fluorescein (G3KL-Fluo) or dansyl (G3KL-Dansyl), which show similar bioactivity profile G3KL. Imaging bacterial killing by super-resolution stimulated emission...
Multi-drug resistant Pseudomonas aeruginosa has increased progressively and impedes further regression in mortality burn patients. Such wound infections serve as bacterial reservoir for nosocomial are associated with significant morbidity costs. Anti-microbial polycationic dendrimers G3KL G3RL, able to kill multi-drug P. aeruginosa, have been previously developed. The combination of these a class biological bandages made progenitor skin cells, which secrete growth factors, could positively...
Abstract C -linked glycosylation is essential for the trafficking, folding and function of secretory transmembrane proteins involved in cellular communication processes. The tryptophan -mannosyltransferase (CMT) enzymes that install modification attach a mannose to first WxxW/C sequons nascent polypeptide chains by an unknown mechanism. Here, we report cryogenic-electron microscopy structures Caenorhabditis elegans CMT four key states: apo, acceptor peptide-bound, donor-substrate...
Zn–proline catalyzed aldolisation of glycoladehyde gave mainly tetroses whereas in the cross-aldolisation and rac-glyceraldehyde, pentoses accounted for 60% sugars formed with 20% ribose.
Abstract The Zn–proline complex is shown to catalyze the aldol reaction of acetone and a wide range arenecarbaldehydes in aqueous media, accepting even deactivated such as methoxybenzaldehydes good yields. Enantiomeric excesses up 56 % could be obtained with 5 mol‐% catalyst at room temperature, 66 –15 °C. regio‐ stereoselective hydroxyacetone (moderate yields) dihydroxyacetone (excellent donor, 80–90 yields mmol‐equiv.). Plausible mechanisms for are discussed. (© Wiley‐VCH Verlag GmbH &...
Zn-proline catalyzes the aldolisation of unprotected glycolaldehyde in water to give tetroses and hexoses; threose (33% product mixture) was formed with 10% enantiomeric excess D-isomer.