Creat membership Creat membership
Sign in

Forgot password?

Confirm
  • Forgot password?
    Sign Up
  • Confirm
    Sign In
home > search

Now showing items 1 - 16 of 20

  • CellFy: A Cell-Based Fragment Screen against C-Type Lectins

    Schulze, Jessica   Baukmann, Hannes   Wawrzinek, Robert   Fuchsberger, Felix F.   Specker, Edgar   Aretz, Jonas   Nazare, Marc   Rademacher, Christoph  

    Fragment-based drug discovery is a powerful complement to conventional high-throughput screening, especially for difficult targets. Screening low-molecular-weight fragments usually requires highly sensitive biophysical methods, because of the generally low affinity of the identified ligands. Here, we developed a cell-based fragment screening assay (cellFy) that allows sensitive identification of fragment hits in a physiologically more relevant environment, in contrast to isolated target screenings in solution. For this, a fluorescently labeled multivalent reporter was employed, enabling direct measurement of displacement by low molecular-weight fragments without requiring enzymatic reactions or receptor activation. We applied this technique to identify hits against two challenging targets of the C-type lectin receptor (CLR) family: Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Nonintegrin (DC-SIGN) and Langerin. Both receptors are involved in pathogen recognition and initiation of an immune response, which renders them attractive targets for immune modulation. Because of their shallow and hydrophilic primary binding site, hit identification for CLRs is challenging and druglike ligands for CLRs are sparse. Screening of a fragment library followed by hit validation identified several promising candidates for further fragment evolution for DC-SIGN. In addition, a multiplexed assay format was developed for simultaneous screening against multiple CLRs, allowing a selectivity counterscreening. Overall, this sensitive cell based fragment screening assay provides a powerful tool for rapid identification of bioactive fragments, even for difficult targets.
    Download Collect
  • Aggregates of diketopyrrolopyrrole dimers in solution

    Wawrzinek, Robert   Zhou, Xiuwen   Ullah, Mujeeb   Namdas, Ebinazar B.   Lo, Shih-Chun  

    Download Collect
  • Mobility Evaluation of BTBT Derivatives: Limitation and Impact on Charge Transport

    Wawrzinek, Robert   Sobus, Jan   Chaudhry, Mujeeb Ullah   Ahmad, Viqar   Grosjean, Arnaud   Clegg, Jack K.   Namdas, Ebinazar B.   Lo, Shih-Chun  

    Download Collect
  • DBD dyes as fluorescent probes for sensing lipophilic environments

    Wawrzinek, Robert   Wessig, Pablo   Moellnitz, Kristian   Nikolaus, Joerg   Schwarzer, Roland   Mueller, Peter   Herrmann, Andreas  

    Small fluorescent organic molecules based on [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD) could be used as probes for lipophillic microenvironments in aqueous solutions by indicating the critical micelles concentration of detergents and staining cell organelles. Their fluorescence lifetime decreases drastically by the amount of water in their direct environment. Therefore they are potential probes for fluorescence lifetime imaging microscopy (FLIM). (C) 2012 Elsevier Ltd. All rights reserved.
    Download Collect
  • On‐Chip Neo‐Glycopeptide Synthesis for Multivalent Glycan Presentation

    Mende, Marco   Tsouka, Alexandra   Heidepriem, Jasmin   Paris, Grigori   Mattes, Daniela S.   Eickelmann, Stephan   Bordoni, Vittorio   Wawrzinek, Robert   Fuchsberger, Felix F.   Seeberger, Peter H.   Rademacher, Christoph   Delbianco, Martina   Mallagaray, Alvaro   Loeffler, Felix F  

    Download Collect
  • Synthesis and spectroscopic properties of a FRET pair based on PPO and DBD dyes

    Wawrzinek, Robert   Wessig, Pablo  

    Highlights • A new FRET pair consisting of PPO as donor and DBD as acceptor has been developed. • Synthesis and spectroscopic properties are presented. • The system exhibits a Förster distance of 2.9 nm and an FRET efficiency of 0.88. • The pseudo Stokes shift of amounts to 190 nm. Abstract A new pair of Förster resonance energy transfer (FRET) performing fluorophores is introduced: An amine functionalized 2,5-diphenyloxazole (PPO) donor tethered via a flexible linker to a carboxylic acid functionalised ester-[1,3]-dioxolo[4.5-f][1,3]benzodioxole (ester DBD) acceptor. Synthesis and spectroscopic properties of this proof-of-concept molecule in acetonitrile are presented and compared to those of its independent chromophores. The system exhibits a Förster distance of 2.9 nm, high FRET efficiency of 0.88 and a pseudo Stokes shift of 190 nm.
    Download Collect
  • DBD Dyes as Fluorescence Lifetime Probes to Study Conformational Changes in Proteins

    Wawrzinek, Robert   Ziomkowska, Joanna   Heuveling, Johanna   Mertens, Monique   Herrmann, Andreas   Schneider, Erwin   Wessig, Pablo  

    Previously, [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD)-based fluorophores used as highly sensitive fluorescence lifetime probes reporting on their microenvironmental polarity have been described. Now, a new generation of DBD dyes has been developed. Although they are still sensitive to polarity, in contrast to the former DBD dyes, they have extraordinary spectroscopic properties even in aqueous surroundings. They are characterized by long fluorescence lifetimes (10-20ns), large Stokes shifts (approximate to 100nm), high photostabilities, and high quantum yields (>0.56). Here, the spectroscopic properties and synthesis of functionalized derivatives for labeling biological targets are described. Furthermore, thio-reactive maleimido derivatives of both DBD generations show strong intramolecular fluorescence quenching. This mechanism has been investigated and is found to undergo a photoelectron transfer (PET) process. After reaction with a thiol group, this fluorescence quenching is prevented, indicating successful bonding. Being sensitive to their environmental polarity, these compounds have been used as powerful fluorescence lifetime probes for the investigation of conformational changes in the maltose ATP-binding cassette transporter through fluorescence lifetime spectroscopy. The differing tendencies of the fluorescence lifetime change for both DBD dye generations promote their combination as a powerful toolkit for studying microenvironments in proteins.
    Download Collect
  • DBD Dyes as Fluorescence Lifetime Probes to Study Conformational Changes in Proteins

    Wawrzinek, Robert   Ziomkowska, Joanna   Heuveling, Johanna   Mertens, Monique   Herrmann, Andreas   Schneider, Erwin   Wessig, Pablo  

    Previously, [1,3]dioxolo[4,5-f][1,3]benzodioxole (DBD)-based fluorophores used as highly sensitive fluorescence lifetime probes reporting on their microenvironmental polarity have been described. Now, a new generation of DBD dyes has been developed. Although they are still sensitive to polarity, in contrast to the former DBD dyes, they have extraordinary spectroscopic properties even in aqueous surroundings. They are characterized by long fluorescence lifetimes (10-20ns), large Stokes shifts (approximate to 100nm), high photostabilities, and high quantum yields (>0.56). Here, the spectroscopic properties and synthesis of functionalized derivatives for labeling biological targets are described. Furthermore, thio-reactive maleimido derivatives of both DBD generations show strong intramolecular fluorescence quenching. This mechanism has been investigated and is found to undergo a photoelectron transfer (PET) process. After reaction with a thiol group, this fluorescence quenching is prevented, indicating successful bonding. Being sensitive to their environmental polarity, these compounds have been used as powerful fluorescence lifetime probes for the investigation of conformational changes in the maltose ATP-binding cassette transporter through fluorescence lifetime spectroscopy. The differing tendencies of the fluorescence lifetime change for both DBD dye generations promote their combination as a powerful toolkit for studying microenvironments in proteins.
    Download Collect
  • Identification of Multiple Druggable Secondary Sites by Fragment Screening against DC-SIGN

    Aretz, Jonas   Baukmann, Hannes   Shanina, Elena   Hanske, Jonas   Wawrzinek, Robert   Zapol'skii, Viktor A.   Seeberger, Peter H.   Kaufmann, Dieter E.   Rademacher, Christoph  

    DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using F-19 NMR spectroscopy and chemical fragment microarrays. Hit validation by SPR and H-1-N-15 HSQC NMR spectroscopy revealed that although no fragment bound in the primary carbohydrate site, five secondary sites are available to harbor drug-like molecules. Building on key interactions of the reported fragment hits, these pockets will be targeted in future approaches to accelerate the development of DC-SIGN inhibitors.
    Download Collect
  • High-Performance,Fullerene-Free Organic Photodiodes Based on a Solution-Processable Indigo

    Kim, Il Ku   Li, Xin   Ullah, Mujeeb   Shaw, Paul E.   Wawrzinek, Robert   Namdas, Ebinazar B.   Lo, Shih-Chun  

    A solution-processable dibromoindigo with an alkyoxyphenyl solubilizing group is developed and used as a new electron acceptor in organic photodiodes. The solution-processed fullerene-free organic photodiodes show an almost spectrally flat response with a high responsivity (0.4 A W-1) and a high detectivity (1 x 10(12) Jones). These values are comparable to silicon-based photodiodes.
    Download Collect
  • Calcium-Independent Activation of an Allosteric Network in Langerin by Heparin Oligosaccharides

    Hanske, Jonas   Wawrzinek, Robert   Geissner, Andreas   Wamhoff, Eike-Christian   Sellrie, Katrin   Schmidt, Henrik   Seeberger, Peter H.   Rademacher, Christoph  

    The C-type lectin receptor Langerin is a glycan-binding protein that serves as an uptake receptor on Langerhans cells and is essential for the formation of Birbeck granules. Whereas most Langerin ligands are recognized by a canonical Ca2+-dependent binding site, heparins have been proposed to make additional contacts to a secondary, Ca2+-independent site. Glycan array screening and biomolecular NMR spectroscopy were employed to investigate the molecular mechanism of these interactions. We observed that binding of heparin hexasaccharides to a secondary site did not require the presence of Ca2+ and activated a previously identified intradomain allosteric network of Langerin (thus far only associated with Ca2+ affinity and release). We propose a communication hub between these two binding sites, which sheds new light on modulatory functions of Langerin-heparin interactions.
    Download Collect
  • A new class of fluorescent dyes based on 1,3-benzodioxole and [1,3]-dioxolo[4.5-f]benzodioxole

    Wessig, Pablo   Wawrzinek, Robert   Moellnitz, Kristian   Feldbusch, Elvira   Schilde, Uwe  

    We report on synthesis and photophysical properties of a new class of fluorescent dyes. They are characterized by large Stokes-shifts, long fluorescence lifetimes in organic solvents and a pronounced dependency of the fluorescence lifetime on the solvent polarity. Also worthy of note is the high bleaching stability. To provide access to biochemical and medical applications a series of derivatives were prepared, which exhibit specific reactivity towards different biologically relevant functional groups (carboxylic acids, amines, maleimides, N-hydroxysuccinimide esters). Furthermore, two alkynes were prepared, which could be used in 'Click' chemistry. (C) 2011 Elsevier Ltd. All rights reserved.
    Download Collect
  • Orange-Red-Light-Emitting Field-Effect Transistors Based on Phosphorescent Pt(II) Complexes with Area Emission

    Wawrzinek, Robert   Muhieddine, Khalid   Ullah, Mujeeb   Koszo, Peter B.   Shaw, Paul E.   Grosjean, Arnaud   Maasoumi, Fatemeh   Stoltzfus, Dani M.   Clegg, Jack K.   Burn, Paul L.   Namdas, Ebinazar B.   Lo, Shih-Chun  

    Two new heteroleptic Pt(II) complexes bearing an n-hexyloxy substituted phenyllepidine-based ligand and either a picolinate (pic) or acetylacetonate (acac) coligand are synthesized for use in organic light-emitting field-effect transistors (LEFETs). Both compounds are obtained in good yields via a short and straightforward synthetic route. It is found that while both Pt(II) complexes show good chemical stability and solubility, the coligand affects the photoluminescence quantum yield and crystal packing of the complexes. Although aggregate induced phosphorescence enhancement is not observed, it is found that high concentrations of the emitters in a poly[bis(4-phenyl) (2,4,6-trimethylphenyl) amine] host lead to improved charge injection in hybrid LEFETs. LEFETs with area emission, high ON/OFF ratios (> 10(6)) and mobilities (approximate to 1.3 cm(2) V-1 s(-1)), and external quantum efficiencies of up to 0.1% at the highest brightness of 855 cd m(-2) are demonstrated.
    Download Collect
  • Orange-Red-Light-Emitting Field-Effect Transistors Based on Phosphorescent Pt(II) Complexes with Area Emission

    Wawrzinek, Robert   Muhieddine, Khalid   Ullah, Mujeeb   Koszo, Peter B.   Shaw, Paul E.   Grosjean, Arnaud   Maasoumi, Fatemeh   Stoltzfus, Dani M.   Clegg, Jack K.   Burn, Paul L.   Namdas, Ebinazar B.   Lo, Shih-Chun  

    Download Collect
  • High Performance p- and n-Type Light-Emitting Field-Effect Transistors Employing Thermally Activated Delayed Fluorescence

    Sobus, Jan   Bencheikh, Fatima   Mamada, Masashi   Wawrzinek, Robert   Ribierre, Jean-Charles   Adachi, Chihaya   Lo, Shih-Chun   Namdas, Ebinazar B.  

    Light-emitting field-effect transistors (LEFETs) are an emerging type of devices that combine light-emitting properties with logical switching function. One of the factors limiting their efficiency stems from the spin statistics of electrically generated excitons. Only 25% of them, short lived singlet states, are capable of light emission, with the other 75% being long lived triplet states that are wasted as heat due to spin-forbidden processes. Traditionally, the way to overcome this limitation is to use phosphorescent materials as additional emission channel harnessing the triplet excitons. Here, an alternative strategy for triplet usage in LEFETs in the form of thermally activated delayed fluorescence (TADF) is presented. Devices employing a TADF capable material, 4CzIPN (2,4,5,6-tetra[9H-carbazol-9-yl]isophthalonitrile), in both n-type and p-type configurations are shown. They manifest excellent electrical characteristics, consistent brightness in the range of 100-1,000 cd m(-2) and external quantum efficiency (EQE) of up to 0.1%, which is comparable to the equivalent organic light-emitting diode (OLED) based on the same materials. Simulation identifies the poor light out-coupling as the main reason for lower than expected EQEs. Transmission measurements show it can be partially alleviated using a more transparent top contact, however more structural optimization is needed to tap the full potential of the device.
    Download Collect
  • Effects of linker and liposome anchoring on lactose-functionalized glycomacromolecules as multivalent ligands for binding galectin-3

    Freichel, Tanja   Laaf, Dominic   Hoffmann, Miriam   Konietzny, Patrick B.   Heine, Viktoria   Wawrzinek, Robert   Rademacher, Christoph   Snyder, Nicole L.   Elling, Lothar   Hartmann, Laura  

    Download Collect
1 2

Contact

If you have any feedback, Please follow the official account to submit feedback.

Turn on your phone and scan

Submit Feedback