A5090200576- Antimicrobial Peptides and Activities
- Antibiotic Resistance in Bacteria
- Chemical Synthesis and Analysis
- RNA Interference and Gene Delivery
- Antimicrobial Resistance in Staphylococcus
- Antimicrobial agents and applications
- Immune Response and Inflammation
- Advanced Drug Delivery Systems
- Microbial Natural Products and Biosynthesis
- Biopolymer Synthesis and Applications
- Carbon dioxide utilization in catalysis
- Chemistry and Chemical Engineering
- Nanoparticle-Based Drug Delivery
- Aquaculture disease management and microbiota
- Bacteriophages and microbial interactions
- Chemical Reactions and Isotopes
- CO2 Reduction Techniques and Catalysts
- Antibiotics Pharmacokinetics and Efficacy
- Synthesis of β-Lactam Compounds
- Peptidase Inhibition and Analysis
University Hospital Heidelberg
2019-2025
Heidelberg University
2019-2025
Robert Bosch (Germany)
2020
Multidrug-resistant bacteria represent one of the biggest challenges facing modern medicine. The increasing prevalence glycopeptide resistance compromises efficacy vancomycin, for a long time considered as last resort treatment resistant bacteria. To reestablish its activity, polycationic peptides were conjugated to vancomycin. By site-specific conjugation, derivatives that bear peptide moiety at four different sites antibiotic synthesized. most potent compounds exhibited an approximately...
Abstract Oral delivery of peptide therapeutics faces multiple challenges due to their instability in the gastrointestinal tract and low permeation capability. In this study, aim is develop a liposomal nanocarrier formulation enable oral vancomycin‐peptide derivative FU002. FU002 promising, resistance‐breaking, antibiotic which exhibits poor bioavailability, limiting its potential therapeutic use. To increase incorporated into tetraether lipid‐stabilized liposomes modified with cyclic...
Abstract The benefit that antibiotics confer to the welfare of mankind is threatened by bacterial resistance. Resistance daptomycin, a cyclic lipopeptide frequently used for treatment complicated bacteremia, prime example this alarming situation. As restricted number antibacterial drug targets limits de novo development, chemical modification existing compounds represents an alternative development option future antimicrobials. This approach involves altering target bacteria through multiple...
Infections caused by multidrug-resistant bacteria are a global emerging problem. New antibiotics that rely on innovative modes of action urgently needed. Ranalexin is potent antimicrobial peptide (AMP) produced in the skin American bullfrog Rana catesbeiana. Despite strong activity against Gram-positive bacteria, ranalexin shows disadvantages such as poor pharmacokinetics. To tackle these problems, derivative consisting exclusively d-amino acids (named danalexin) was synthesized and compared...
Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, only a few compounds capable serving as last resort severe infections. Therefore, approaches to control multidrug-resistant must be implemented. Here, strategy reactivating established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation overcome resistance was...
The increasing number of infections caused by multidrug-resistant bacteria requires an intensified search for new antibiotics. Pep19-4LF is a synthetic antimicrobial peptide (GKKYRRFRWKFKGKLFLFG) that was previously designed with the main focus on high activity. hydrophobic motif, LFLFG, found to be essential However, this motif shows several limitations such as aggregation in biological media, low solubility, and small yields synthesis. In order obtain more appropriate characteristics,...
The number of approved macromolecular drugs such as peptides, proteins and antibodies steadily increases. Since with high molecular weight are commonly not suitable for oral delivery, research on carrier strategies enabling administration is vital interest. In past decades, nanocarriers, in particular liposomes, have been exhaustively investigated drug-delivery platform. Despite their successful application parenteral delivery vehicles, liposomes up to date succeeded administration. However,...
Antibiotic resistance still represents a global health concern which diminishes the pool of effective antibiotics. With vancomycin derivative FU002, we recently reported highly potent substance active against Gram-positive bacteria with potential to overcome resistance. However, translation its excellent antimicrobial activity into clinical efficiency could be hampered by rapid elimination from blood stream. To improve pharmacokinetics, encapsulated FU002 in PEGylated liposomes. For...
As multidrug-resistant bacteria represent a concerning burden, experts insist on the need for dramatic rethinking antibiotic use and development in order to avoid post-antibiotic era. New rapidly developable strategies antimicrobial substances, particular substances highly potent against bacteria, are urgently required. Some of treatment options currently available considerably limited by side effects unfavorable pharmacokinetics. The glycopeptide vancomycin is considered an last resort. Its...
Abstract Antibiotic‐resistant enterococci represent a significant global health challenge. Unfortunately, most β‐lactam antibiotics are not applicable for enterococcal infections due to intrinsic resistance. To extend their antimicrobial spectrum, polycationic peptides conjugated examples from each of the four classes antibiotics. Remarkably, β‐lactam–peptide conjugates gained an up 1000‐fold increase in activity against vancomycin‐susceptible and vancomycin‐resistant enterococci. Even...
Abstract Die zunehmende Prävalenz von Resistenzen bei Bakterien gegen Glykopeptid‐Antibiotika macht auch vor Vancomycin nicht halt. Um die ursprünglich hohe Effektivität diese resistenten wieder zu erzielen, wurden hier polykationische Peptide an gekuppelt. Mithilfe einer regioselektiven Konjugationsstrategie zahlreiche Derivate synthetisiert, welche Peptidmodifikation vier unterschiedlichen Anknüpfungsstellen des Antibiotikums tragen. hierbei erhaltenen wirksamsten Verbindungen zeigten eine...
Bakterielle Resistenzen drohen, die Errungenschaften der Antibiotikatherapie zunichte zu machen. Wie P. Uhl et al. in ihrer Zuschrift auf S. 8908 erläutern, konnte am Klinikum Heidelberg mit Peptid-Konjugaten eine tausendfache Aktivitätssteigerung des Reserveantibiotikums Vancomycin erreicht werden. Dieser Ansatz offenbart das Potential chemischen Modifizierung bewährter Naturstoffe als Alternative zur aufwendigen De-novo-Wirkstoffentwicklung von Wirkstoffen.
The interpretation of the chemical bond in NaBH 3À as a dative Na À !BH 3 proposed by Liu et al. is questioned.The dissociation products are and BH but nature changes during formation from interactions at long distances to an electronsharing equilibrium geometry.