Daniel Lauster
Humboldt University of Berlin
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Daniel Lauster.
PLOS ONE | 2016
Henry Memczak; Daniel Lauster; Parimal Kar; Santiago Di Lella; Rudolf Volkmer; Volker Knecht; Andreas Herrmann; Eva Ehrentreich-Förster; Frank F. Bier; Walter F. M. Stöcklein
Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/Mute Swan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.
Beilstein Journal of Organic Chemistry | 2015
Daniel Lauster; Damian Pawolski; Julian Storm; Kai Ludwig; Rudolf Volkmer; Henry Memczak; Andreas Herrmann; Sumati Bhatia
Summary For antiviral drug design, especially in the field of influenza virus research, potent multivalent inhibitors raise high expectations for combating epidemics and pandemics. Among a large variety of covalent and non-covalent scaffold systems for a multivalent display of inhibitors, we created a simple supramolecular platform to enhance the antiviral effect of our recently developed antiviral Peptide B (PeBGF), preventing binding of influenza virus to the host cell. By conjugating the peptide with stearic acid to create a higher-order structure with a multivalent display, we could significantly enhance the inhibitory effect against the serotypes of both human pathogenic influenza virus A/Aichi/2/1968 H3N2, and avian pathogenic A/FPV/Rostock/34 H7N1 in the hemagglutination inhibition assay. Further, the inhibitory potential of stearylated PeBGF (C18-PeBGF) was investigated by infection inhibition assays, in which we achieved low micromolar inhibition constants against both viral strains. In addition, we compared C18-PeBGF to other published amphiphilic peptide inhibitors, such as the stearylated sugar receptor mimicking peptide (Matsubara et al. 2010), and the “Entry Blocker” (EB) (Jones et al. 2006), with respect to their antiviral activity against infection by Influenza A Virus (IAV) H3N2. However, while this strategy seems at a first glance promising, the native situation is quite different from our experimental model settings. First, we found a strong potential of those peptides to form large amyloid-like supramolecular assemblies. Second, in vivo, the large excess of cell surface membranes provides an unspecific target for the stearylated peptides. We show that acylated peptides insert into the lipid phase of such membranes. Eventually, our study reveals serious limitations of this type of self-assembling IAV inhibitors.
Angewandte Chemie | 2017
Daniel Lauster; Maria Glanz; Markus Bardua; Kai Ludwig; Markus Hellmund; Ute Hoffmann; Alf Hamann; Christoph Böttcher; Rainer Haag; Christian P. R. Hackenberger; Andreas Herrmann
Abstract To inhibit binding of the influenza A virus to the host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles binding with nanomolar affinity to the virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide–polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non‐carbohydrate‐based, covalently linked, multivalent virus inhibitor in the nano‐ to picomolar range by ensuring low peptide‐ligand density on a larger dendritic scaffold.
Small | 2018
Ievgen S. Donskyi; Moritz Drüke; Kim Silberreis; Daniel Lauster; Kai Ludwig; Christian Kühne; Wolfgang E. S. Unger; Christoph Böttcher; Andreas Herrmann; Jens Dernedde; Mohsen Adeli; Rainer Haag
Understanding the mechanism of interactions of nanomaterials at biointerfaces is a crucial issue to develop new antimicrobial vectors. In this work, a series of water-soluble fullerene-polyglycerol sulfates (FPS) with different fullerene/polymer weight ratios and varying numbers of polyglycerol sulfate branches are synthesized, characterized, and their interactions with two distinct surfaces displaying proteins involved in target cell recognition are investigated. The combination of polyanionic branches with a solvent exposed variable hydrophobic core in FPS proves to be superior to analogs possessing only one of these features in preventing interaction of vesicular stomatitis virus coat glycoprotein (VSV-G) with baby hamster kidney cells serving as a model of host cell. Interference with L-selectin-ligand binding is dominated by the negative charge, which is studied by two assays: a competitive surface plasmon resonance (SPR)-based inhibition assay and the leukocyte cell (NALM-6) rolling on ligands under flow conditions. Due to possible intrinsic hydrophobic and electrostatic effects of synthesized compounds, pico- to nanomolar half maximal inhibitory concentrations (IC50 ) are achieved. With their highly antiviral and anti-inflammatory properties, together with good biocompatibility, FPS are promising candidates for the future development towards biomedical applications.
Chemistry: A European Journal | 2018
Rainer Haag; Pallavi Kiran; Sumati Bhatia; Daniel Lauster; Stevan Aleksić; Carsten Fleck; Natalija Peric; Wolfgang Maison; Susanne Liese; Bettina Keller; Andreas Herrmann
Abstract Herein, the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31 is described. Although the flexible Tris‐based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a rigid adamantane core dominated flexible tripodal compounds with micromolar binding and hemagglutination inhibition constants. Simulation studies indicated increased conformational penalties for long OEG spacers. Using a systematic approach with molecular modeling and simulations as well as biophysical analysis, these findings emphasize on the importance of the scaffold rigidity and the challenges associated with the spacer length optimization.
Journal of the American Chemical Society | 2017
Victor Bandlow; Susanne Liese; Daniel Lauster; Kai Ludwig; Roland R. Netz; Andreas Herrmann; Oliver Seitz
Attachment of the Influenza A virus onto host cells involves multivalent interactions between virus surface hemagglutinin (HA) and sialoside-containing glyco ligands. Despite the development of extremely powerful multivalent binders of the Influenza virus and other viruses, comparably little is known about the optimal spacing of HA ligands, which ought to bridge binding sites within or across the trimeric HA molecules. To explore the criteria for ligand economical high affinity binding, we systematically probed distance-affinity relationships by means of two differently behaving scaffold types based on (i) flexible polyethylene glycol (PEG) conjugates and (ii) rigid self-assembled DNA·PNA complexes. The bivalent scaffolds presented two sialyl-LacNAc ligands in 23-101 Å distance. A combined analysis of binding by means of microscale thermophoresis measurements and statistical mechanics models exposed the inherent limitations of PEG-based spacers. Given the distance requirements of HA, the flexibility of PEG scaffolds is too high to raise the effective concentration of glyco ligands above a value that allows interactions with the low affinity binding site. By contrast, spatial screening with less flexible, self-assembled peptide nucleic acid (PNA)·DNA complexes uncovered a well-defined and, surprisingly, bimodal distance-affinity relationship for interactions of the Influenza A virus HA with bivalent displays of the natural sialyl-LacNAc ligand. Optimal constructs conferred 103-fold binding enhancements with only two ligands. We discuss the existence of secondary binding sites and shine light on the preference for intramolecular rather than intermolecular recognition of HA trimers on the virus surface.
ChemBioChem | 2015
Daniel Lauster; Olalla Vázquez; Roland Schwarzer; Oliver Seitz; Andreas Herrmann
We have established a method of preparing giant plasma membrane vesicles (GPMVs) by using cysteine mutants of the proapoptotic peptide (PAP) Ac‐R7‐GG‐KLAKLAKKLAKLAK. A cysteine scan revealed that cytotoxicity and GPMV formation were dependent on the cysteine position within the PAP sequence. In comparison to GPMVs prepared by extensive treatment with paraformaldehyde (PFA) and dithiothreitol (DTT), our GPMVs were produced from HeLa cells at much lower concentrations of the blebbing agent. We found that only GPMVs derived from cysteine‐containing PAP showed lipid phase separation. This membrane model was applied to investigate the phase partitioning of two relevant membrane proteins: influenza virus hemagglutinin (HA) and tetherin, which clamps budding HIV to infected cells. For tetherin, we show for the first time exclusion from cholesterol‐rich domains in a GPMV model, thus documenting the potential of our approach for membrane‐partitioning studies.
Advanced Functional Materials | 2017
Mohammad Fardin Gholami; Daniel Lauster; Kai Ludwig; Julian Storm; Benjamin Ziem; Nikolai Severin; Christoph Böttcher; Jürgen P. Rabe; Andreas Herrmann; Mohsen Adeli; Rainer Haag
Biomaterials | 2017
Sumati Bhatia; Daniel Lauster; Markus Bardua; Kai Ludwig; Stefano Angioletti-Uberti; Nicole Popp; Ute Hoffmann; Florian Paulus; Matthias Budt; Marlena Stadtmüller; Thorsten Wolff; Alf Hamann; Christoph Böttcher; Andreas Herrmann; Rainer Haag
Angewandte Chemie | 2017
Daniel Lauster; Maria Glanz; Markus Bardua; Kai Ludwig; Markus Hellmund; Ute Hoffmann; Alf Hamann; Christoph Böttcher; Rainer Haag; Christian P. R. Hackenberger; Andreas Herrmann