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End date: 2022 × Start date: 2022 × DDC: 540 × Has files: Yes × WGL Institute: DWI ×

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Now showing 1 - 10 of 72
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    Controlling Optical and Catalytic Activity of Genetically Engineered Proteins by Ultrasound
    (Weinheim : Wiley-VCH, 2021) Zhou, Yu; Huo, Shuaidong; Loznik, Mark; Göstl, Robert; Boersma, Arnold J.; Herrmann, Andreas
    Ultrasound (US) produces cavitation-induced mechanical forces stretching and breaking polymer chains in solution. This type of polymer mechanochemistry is widely used for synthetic polymers, but not biomacromolecules, even though US is biocompatible and commonly used for medical therapy as well as in vivo imaging. The ability to control protein activity by US would thus be a major stepping-stone for these disciplines. Here, we provide the first examples of selective protein activation and deactivation by means of US. Using GFP as a model system, we engineer US sensitivity into proteins by design. The incorporation of long and highly charged domains enables the efficient transfer of force to the protein structure. We then use this principle to activate the catalytic activity of trypsin by inducing the release of its inhibitor. We expect that this concept to switch “on” and “off” protein activity by US will serve as a blueprint to remotely control other bioactive molecules. © 2020 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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    Plasmonic Hepatitis B Biosensor for the Analysis of Clinical Saliva
    (Columbus, Ohio : American Chemical Society, 2017) Riedel, Tomáš; Hageneder, Simone; Surman, František; Pop-Georgievski, Ognen; Noehammer, Christa; Hofner, Manuela; Brynda, Eduard; Rodriguez-Emmenegger, Cesar; Dostálek, Jakub
    A biosensor for the detection of hepatitis B antibodies in clinical saliva was developed. Compared to conventional analysis of blood serum, it offers the advantage of noninvasive collection of samples. Detection of biomarkers in saliva imposes two major challenges associated with the low analyte concentration and increased surface fouling. The detection of minute amounts of hepatitis B antibodies was performed by plasmonically amplified fluorescence sandwich immunoassay. To have access to specific detection, we prevented the nonspecific adsorption of biomolecules present in saliva by brushes of poly[(N-(2-hydroxypropyl) methacrylamide)-co-(carboxybetaine methacrylamide)] grafted from the gold sensor surface and post modified with hepatitis B surface antigen. Obtained results were validated against the response measured with ELISA at a certified laboratory using serum from the same patients. © 2017
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    Activation of the Catalytic Activity of Thrombin for Fibrin Formation by Ultrasound
    (Weinheim : Wiley-VCH, 2021) Zhao, Pengkun; Huo, Shuaidong; Fan, Jilin; Chen, Junlin; Kiessling, Fabian; Boersma, Arnold J.; Göstl, Robert; Herrmann, Andreas
    The regulation of enzyme activity is a method to control biological function. We report two systems enabling the ultrasound-induced activation of thrombin, which is vital for secondary hemostasis. First, we designed polyaptamers, which can specifically bind to thrombin, inhibiting its catalytic activity. With ultrasound generating inertial cavitation and therapeutic medical focused ultrasound, the interactions between polyaptamer and enzyme are cleaved, restoring the activity to catalyze the conversion of fibrinogen into fibrin. Second, we used split aptamers conjugated to the surface of gold nanoparticles (AuNPs). In the presence of thrombin, these assemble into an aptamer tertiary structure, induce AuNP aggregation, and deactivate the enzyme. By ultrasonication, the AuNP aggregates reversibly disassemble releasing and activating the enzyme. We envision that this approach will be a blueprint to control the function of other proteins by mechanical stimuli in the sonogenetics field. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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    Anti-Stokes Stress Sensing: Mechanochemical Activation of Triplet-Triplet Annihilation Photon Upconversion
    (Weinheim : Wiley-VCH, 2019) Yildiz, Deniz; Baumann, Christoph; Mikosch, Annabel; Kuehne, Alexander J.C.; Herrmann, Andreas; Göstl, Robert
    The development of methods to detect damage in macromolecular materials is of paramount importance to understand their mechanical failure and the structure–property relationships of polymers. Mechanofluorophores are useful and sensitive molecular motifs for this purpose. However, to date, tailoring of their optical properties remains challenging and correlating emission intensity to force induced material damage and the respective events on the molecular level is complicated by intrinsic limitations of fluorescence and its detection techniques. Now, this is tackled by developing the first stress-sensing motif that relies on photon upconversion. By combining the Diels–Alder adduct of a π-extended anthracene with the porphyrin-based triplet sensitizer PtOEP in polymers, triplet–triplet annihilation photon upconversion of green to blue light is mechanochemically activated in solution as well as in the solid state. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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    Multicolor Mechanofluorophores for the Quantitative Detection of Covalent Bond Scission in Polymers
    (Weinheim : Wiley-VCH, 2021) Baumann, Christoph; Stratigaki, Maria; Centeno, Silvia P.; Göstl, Robert
    The fracture of polymer materials is a multiscale process starting with the scission of a single molecular bond advancing to a site of failure within the bulk. Quantifying the bonds broken during this process remains a big challenge yet would help to understand the distribution and dissipation of macroscopic mechanical energy. We here show the design and synthesis of fluorogenic molecular optical force probes (mechanofluorophores) covering the entire visible spectrum in both absorption and emission. Their dual fluorescent character allows to track non-broken and broken bonds in dissolved and bulk polymers by fluorescence spectroscopy and microscopy. Importantly, we develop an approach to determine the absolute number and relative fraction of intact and cleaved bonds with high local resolution. We anticipate that our mechanofluorophores in combination with our quantification methodology will allow to quantitatively describe fracture processes in materials ranging from soft hydrogels to high-performance polymers. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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    Polymer Brush-Functionalized Chitosan Hydrogels as Antifouling Implant Coatings
    (Columbus, Ohio : American Chemical Society, 2017) Buzzacchera, Irene; Vorobii, Mariia; Kostina, Nina Yu; de Los Santos Pereira, Andres; Riedel, Tomáš; Bruns, Michael; Ogieglo, Wojciech; Möller, Martin; Wilson, Christopher J.; Rodriguez-Emmenegger, Cesar
    Implantable sensor devices require coatings that efficiently interface with the tissue environment to mediate biochemical analysis. In this regard, bioinspired polymer hydrogels offer an attractive and abundant source of coating materials. However, upon implantation these materials generally elicit inflammation and the foreign body reaction as a consequence of protein fouling on their surface and concomitant poor hemocompatibility. In this report we investigate a strategy to endow chitosan hydrogel coatings with antifouling properties by the grafting of polymer brushes in a "grafting-from" approach. Chitosan coatings were functionalized with polymer brushes of oligo(ethylene glycol) methyl ether methacrylate and 2-hydroxyethyl methacrylate using photoinduced single electron transfer living radical polymerization and the surfaces were thoroughly characterized by XPS, AFM, water contact angle goniometry, and in situ ellipsometry. The antifouling properties of these new bioinspired hydrogel-brush coatings were investigated by surface plasmon resonance. The influence of the modifications to the chitosan on hemocompatibility was assessed by contacting the surfaces with platelets and leukocytes. The coatings were hydrophilic and reached a thickness of up to 180 nm within 30 min of polymerization. The functionalization of the surface with polymer brushes significantly reduced the protein fouling and eliminated platelet activation and leukocyte adhesion. This methodology offers a facile route to functionalizing implantable sensor systems with antifouling coatings that improve hemocompatibility and pave the way for enhanced device integration in tissue.
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    Mechanochemical Release of Non-Covalently Bound Guests from a Polymer-Decorated Supramolecular Cage
    (Weinheim : Wiley-VCH, 2021) Küng, Robin; Pausch, Tobias; Rasch, Dustin; Göstl, Robert; Schmidt, Bernd M.
    Supramolecular coordination cages show a wide range of useful properties including, but not limited to, complex molecular machine-like operations, confined space catalysis, and rich host–guest chemistries. Here we report the uptake and release of non-covalently encapsulated, pharmaceutically-active cargo from an octahedral Pd cage bearing polymer chains on each vertex. Six poly(ethylene glycol)-decorated bipyridine ligands are used to assemble an octahedral PdII6(TPT)4 cage. The supramolecular container encapsulates progesterone and ibuprofen within its hydrophobic nanocavity and is activated by shear force produced by ultrasonication in aqueous solution entailing complete cargo release upon rupture, as shown by NMR and GPC analyses. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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    Less Unfavorable Salt Bridges on the Enzyme Surface Result in More Organic Cosolvent Resistance
    (Weinheim : Wiley-VCH, 2021) Cui, Haiyang; Eltoukhy, Lobna; Zhang, Lingling; Markel, Ulrich; Jaeger, Karl-Erich; Davari, Mehdi D.; Schwaneberg, Ulrich
    Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co-)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6-fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137-fold, and half-life up to 3.3-fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50–100 °C. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs- and/or thermal-resistant lipases and other α/β-hydrolases. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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    Significant Upregulation of Alzheimer's β-Amyloid Levels in a Living System Induced by Extracellular Elastin Polypeptides
    (Weinheim : Wiley-VCH, 2019) Ma, Chao; Su, Juanjuan; Sun, Yao; Feng, Yang; Shen, Nolan; Li, Bo; Liang, Yingxia; Yang, Xintong; Wu, Hui; Zhang, Hongjie; Herrmann, Andreas; Tanzi, Rudolph E.; Liu, Kai; Zhang, Can
    Alzheimer's disease (AD) is a neurodegenerative disorder and the primary cause of age-related dementia. The etiology of AD is complex and has not been completely elucidated. Herein, we report that treatment with elastin-like polypeptides (ELPs), a component of the brain extracellular matrix (ECM), significantly increased the levels of AD-related amyloid-β peptides (Aβ) both in vitro and in vivo. Regarding the molecular mechanism(s), the upregulation of Aβ levels was related to increased proteolytic processing of the amyloid precursor protein. Furthermore, nesting tests demonstrated that the ELP-treated animals showed significant neurobehavioral deficits with cognitive impairment. These results suggest that the elastin is associated with AD-related pathological and behavioral changes. This finding presents a new aspect for Alzheimer's amyloidosis event and provides a great promise in developing ELP-based model systems to better understand the pathogenesis of AD. © 2019
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    Enhanced Concanavalin A Binding to Preorganized Mannose Nanoarrays in Glycodendrimersomes Revealed Multivalent Interactions
    (Weinheim : Wiley-VCH, 2021) Kostina, Nina Yu; Söder, Dominik; Haraszti, Tamás; Xiao, Qi; Rahimi, Khosrow; Partridge, Benjamin E.; Klein, Michael L.; Percec, Virgil; Rodriguez‐Emmenegger, Cesar
    The effect of the two-dimensional glycan display on glycan-lectin recognition remains poorly understood despite the importance of these interactions in a plethora of cellular processes, in (patho)physiology, as well as its potential for advanced therapeutics. Faced with this challenge we utilized glycodendrimersomes, a type of synthetic vesicles whose membrane mimics the surface of a cell and offers a means to probe the carbohydrate biological activity. These single-component vesicles were formed by the self-assembly of sequence-defined mannose-Janus dendrimers, which serve as surrogates for glycolipids. Using atomic force microscopy and molecular modeling we demonstrated that even mannose, a monosaccharide, was capable of organizing the sugar moieties into periodic nanoarrays without the need of the formation of liquid-ordered phases as assumed necessary for rafts. Kinetics studies of Concanavalin A binding revealed that those nanoarrays resulted in a new effective ligand yielding a ten-fold increase in the kinetic and thermodynamic constant of association. © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH