0000000000010388
AUTHOR
Matthias Konhäuser
Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristics.
Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on…
Xylochemical Synthesis of Cytotoxic 2-Aminophenoxazinone-Type Natural Products Through Oxidative Cross Coupling
Today, the total synthesis of natural products mostly relies on the use of petroleum-based starting materials. The commercial availability of building blocks of this type often deflects attention away from lengthy synthetic routes required for the reintroduction of heteroatom substitution patterns lost in the geological process of kerogenesis. Herein, the use of wood-based starting materials, the so-called xylochemicals, for the synthesis of 2-aminophenoxazinone natural products is presented. The inherent heteroatom substitution patterns as well as chemical functionalities were employed and permitted a short and straightforward synthetic strategy. Moreover, a novel and “green” method for co…
Double stimuli-responsive polysaccharide block copolymers as green macrosurfactants for near-infrared photodynamic therapy
The NIR absorbing photosensitizer phthalocyanine zinc (PC(Zn)) was stabilized in aqueous media as water-dispersible nanoparticles with a reduction- and pH-responsive full polysaccharide block copolymer. A cellular uptake and also photo switchable intracellular activity of the cargo upon irradiation at wavelengths in the near infrared region were shown. The block copolymer was synthesized by applying a copper-free click strategy based on a thiol exchange reaction, creating an amphiphilic double-stimuli-responsive mixed disulfide. The dual-sensitive polysaccharide micelles represent a non-toxic and biodegradable green macrosurfactant for the delivery of phthalocyanine zinc. By encapsulation i…
Asymmetric Disulfanylbenzamides as Irreversible and Selective Inhibitors of Staphylococcus aureus Sortase A
Abstract Staphylococcus aureus is one of the most frequent causes of nosocomial and community‐acquired infections, with drug‐resistant strains being responsible for tens of thousands of deaths per year. S. aureus sortase A inhibitors are designed to interfere with virulence determinants. We have identified disulfanylbenzamides as a new class of potent inhibitors against sortase A that act by covalent modification of the active‐site cysteine. A broad series of derivatives were synthesized to derive structure‐activity relationships (SAR). In vitro and in silico methods allowed the experimentally observed binding affinities and selectivities to be rationalized. The most active compounds were f…