Filters

2017 - 20204

More filters

2021 - 20234
Reset filters

Settings

Author: Rahimi, Khosrow × End date: 2024 × Start date: 2020 × DDC: 500 × Type: article × WGL Institute: DWI ×

Search Results

Now showing 1 - 4 of 4
  • Thumbnail Image
    Item
    Nanovesicles displaying functional linear and branched oligomannose self-assembled from sequence-defined Janus glycodendrimers
    (Washington, DC : NAS, 2020) Xiao, Qi; Delbianco, Martina; Sherman, Samuel E.; Reveron Perez, Aracelee M.; Bharate, Priya; Pardo-Vargas, Alonso; Rodriguez-Emmenegger, Cesar; Kostina, Nina Yu; Rahimi, Khosrow; Söder, Dominik; Möller, Martin; Klein, Michael L.; Seeberger, Peter H.; Percec, Virgil
    Cell surfaces are often decorated with glycoconjugates that contain linear and more complex symmetrically and asymmetrically branched carbohydrates essential for cellular recognition and communication processes. Mannose is one of the fundamental building blocks of glycans in many biological membranes. Moreover, oligomannoses are commonly found on the surface of pathogens such as bacteria and viruses as both glycolipids and glycoproteins. However, their mechanism of action is not well understood, even though this is of great potential interest for translational medicine. Sequence-defined amphiphilic Janus glycodendrimers containing simple mono- and disaccharides that mimic glycolipids are known to self-assemble into glycodendrimersomes, which in turn resemble the surface of a cell by encoding carbohydrate activity via supramolecular multivalency. The synthetic challenge of preparing Janus glycodendrimers containing more complex linear and branched glycans has so far prevented access to more realistic cell mimics. However, the present work reports the use of an isothiocyanate-amine “click”-like reaction between isothiocyanate-containing sequence-defined amphiphilic Janus dendrimers and either linear or branched oligosaccharides containing up to six monosaccharide units attached to a hydrophobic amino-pentyl linker, a construct not expected to assemble into glycodendrimersomes. Unexpectedly, these oligoMan-containing dendrimers, which have their hydrophobic linker connected via a thiourea group to the amphiphilic part of Janus glycodendrimers, self-organize into nanoscale glycodendrimersomes. Specifically, the mannose-binding lectins that best agglutinate glycodendrimersomes are those displaying hexamannose. Lamellar “raft-like” nanomorphologies on the surface of glycodendrimersomes, self-organized from these sequence-defined glycans, endow these membrane mimics with high biological activity. © 2020 National Academy of Sciences. All rights reserved.
  • Thumbnail Image
    Item
    Design–functionality relationships for adhesion/growth-regulatory galectins
    (Washington, DC : National Acad. of Sciences, 2019) Ludwig, Anna-Kristin; Michalak, Malwina; Xiao, Qi; Gilles, Ulrich; Medrano, Francisco J.; Ma, Hanyue; FitzGerald, Forrest G.; Hasley, William D.; Melendez-Davila, Adriel; Liu, Matthew; Rahimi, Khosrow; Kostina, Nina Yu; Rodriguez-Emmenegger, Cesar; Möller, Martin; Lindner, Ingo; Kaltner, Herbert; Cudic, Mare; Reusch, Dietmar; Kopitz, Jürgen; Romero, Antonio; Oscarson, Stefan; Klein, Michael L.; Gabius, Hans-Joachim; Percec, Virgil
    Glycan-lectin recognition is assumed to elicit its broad range of (patho)physiological functions via a combination of specific contact formation with generation of complexes of distinct signal-triggering topology on biomembranes. Faced with the challenge to understand why evolution has led to three particular modes of modular architecture for adhesion/growth-regulatory galectins in vertebrates, here we introduce protein engineering to enable design switches. The impact of changes is measured in assays on cell growth and on bridging fully synthetic nanovesicles (glycodendrimersomes) with a chemically programmable surface. Using the example of homodimeric galectin-1 and monomeric galectin-3, the mutual design conversion caused qualitative differences, i.e., from bridging effector to antagonist/from antagonist to growth inhibitor and vice versa. In addition to attaining proof-of-principle evidence for the hypothesis that chimera-type galectin-3 design makes functional antagonism possible, we underscore the value of versatile surface programming with a derivative of the pan-galectin ligand lactose. Aggregation assays with N,N′-diacetyllactosamine establishing a parasite-like surface signature revealed marked selectivity among the family of galectins and bridging potency of homodimers. These findings provide fundamental insights into design-functionality relationships of galectins. Moreover, our strategy generates the tools to identify biofunctional lattice formation on biomembranes and galectin-reagents with therapeutic potential.
  • Thumbnail Image
    Item
    Cubosomes from hierarchical self-assembly of poly(ionic liquid) block copolymers
    ([London] : Nature Publishing Group UK, 2017) He, Hongkun; Rahimi, Khosrow; Zhong, Mingjiang; Mourran, Ahmed; Luebke, David R.; Nulwala, Hunaid B.; Möller, Martin; Matyjaszewski, Krzysztof
    Cubosomes are micro- and nanoparticles with a bicontinuous cubic two-phase structure, reported for the self-assembly of low molecular weight surfactants, for example, lipids, but rarely formed by polymers. These objects are characterized by a maximum continuous interface and high interface to volume ratio, which makes them promising candidates for efficient adsorbents and host-guest applications. Here we demonstrate self-assembly to nanoscale cuboidal particles with a bicontinuous cubic structure by amphiphilic poly(ionic liquid) diblock copolymers, poly(acrylic acid)-block-poly(4-vinylbenzyl)-3-butyl imidazolium bis(trifluoromethylsulfonyl)imide, in a mixture of tetrahydrofuran and water under optimized conditions. Structure determining parameters include polymer composition and concentration, temperature, and the variation of the solvent mixture. The formation of the cubosomes can be explained by the hierarchical interactions of the constituent components. The lattice structure of the block copolymers can be transferred to the shape of the particle as it is common for atomic and molecular faceted crystals.
  • Thumbnail Image
    Item
    Encapsulation of hydrophobic components in dendrimersomes and decoration of their surface with proteins and nucleic acids
    (Washington, DC : National Acad. of Sciences, 2019) Torre, Paola; Xiao, Qi; Buzzacchera, Irene; Sherman, Samuel E.; Rahimi, Khosrow; Kostina, Nina Yu.; Rodriguez-Emmenegger, Cesar; Möller, Martin; Wilson, Christopher J.; Klein, Michael L.; Good, Matthew C.; Percec, Virgil
    Reconstructing the functions of living cells using nonnatural components is one of the great challenges of natural sciences. Compartmentalization, encapsulation, and surface decoration of globular assemblies, known as vesicles, represent key early steps in the reconstitution of synthetic cells. Here we report that vesicles self-assembled from amphiphilic Janus dendrimers, called dendrimersomes, encapsulate high concentrations of hydrophobic components and do so more efficiently than commercially available stealth liposomes assembled from phospholipid components. Multilayer onion-like dendrimersomes demonstrate a particularly high capacity for loading low-molecular weight compounds and even folded proteins. Coassembly of amphiphilic Janus dendrimers with metal-chelating ligands conjugated to amphiphilic Janus dendrimers generates dendrimersomes that selectively display folded proteins on their periphery in an oriented manner. A modular strategy for tethering nucleic acids to the surface of dendrimersomes is also demonstrated. These findings augment the functional capabilities of dendrimersomes to serve as versatile biological membrane mimics.