Papers by Thisbe Lindhorst
Chemie in Unserer Zeit, Apr 1, 2016
Angewandte Chemie, Aug 10, 2017
Nachrichten aus der Chemie
VV Die GDCh hat ein besonderes Jahr hinter sich denn 2017 stand ganz im Zeichen des 150-Jahre-Jub... more VV Die GDCh hat ein besonderes Jahr hinter sich denn 2017 stand ganz im Zeichen des 150-Jahre-Jubiläums. Ich habe in einer monatlichen Kolumne von April 2016 bis Januar 2017 das Jubiläum mit verschiedenen Gedanken und Themen verbunden, um Sie, liebe Kolleginnen und Kollegen für das Jubiläumsjahr zu motivieren. Vieles davon hat in der Mitgliedschaft Nachhall gefunden, und das hat mich gefreut. Nur wenn die Mitglieder mitdenken und an ihrer Fachgesellschaft Anteil nehmen, sind wir eine lebendige Gemeinschaft. Jetzt im Dezember schauen wir zurück auf viele fulminante Veranstaltungen, ganz zuvorderst das GDCh Wissenschaftsforum Chemie vom 10. bis 14. September in Berlin. Zum ersten Mal war das "Experiment Zukunft -Wertedenken in der Chemie" mit dabei und das Satellitensymposium "Das Undenkbare denken". Damit haben wir etwas Neues gewagt und neue Ideen in Umlauf gebracht. Nun bleibt die Aufgabe, diese Impulse unseres überaus gelungenen und facettenreichen ChemieFestes und seiner besonderen Formate für unsere Gesellschaft zu nutzen. Den Erfolg sollten wir als Rückenwind für die Reise in kommende Jahre verwenden. Denn die Zeiten werden wohl kaum einfacher werden. In den zwei Jahren, in denen ich Ihre Präsidentin sein durfte, hat sich die Welt stark verändert. Wissenschaftliche Wahrheitssuche wird inzwischen von vielen Menschen und sogar Staatenlenkern als irrelevant oder gar als Attrappe, als "Fake" verunglimpft. Und so muss auch die GDCh in eine Zukunft navigieren, in der die chemische Wissenschaft mehr denn je um das Vertrauen der Gesellschaft werben muss. Außerdem sind wir mit einer Situation konfrontiert, in der die Menschen in jeder Sekunde einer Fülle von Breaking News und Informationen ausgesetzt sind und eine Fachwissenschaft nicht mit einem aufmerksamen oder a priori interessierten Publikum rechnen kann. Wie kann sich Wissenschaft jetzt verhalten? FAZ-Herausgeber Jürgen Kaube sprach auf
Scientific Reports
Following the reaction of biological membranes to external stimuli reveals fundamental insights i... more Following the reaction of biological membranes to external stimuli reveals fundamental insights into cellular function. Here, self-assembled lipid monolayers act as model membranes containing photoswitchable azobenzene glycolipids for investigating structural response during isomerization by combining Langmuir isotherms with X-ray scattering. Controlled in-situ trans/cis photoswitching of the azobenzene N = N double bond alters the DPPC monolayer structure, causing reproducible changes in surface pressure and layer thickness, indicating monolayer reorientation. Interestingly, for monolayers containing azobenzene glycolipids, along with the expected DPPC phase transitions an additional discontinuity is observed. The associated reorintation represents a crossover point, with the surface pressure and layer thickness changing in opposite directions above and below. This is evidence that the azobenzene glycolipids themselves change orientation within the monolayer. Such behaviour suggest...
Synthesis of regioisomeric maltose-based Man/Glc glycoclusters to control glycoligand presentation in 3D space
Organic & Biomolecular Chemistry
Regioisomeric maltose-based heterobivalent glycoclusters were designed to tease out the effect of... more Regioisomeric maltose-based heterobivalent glycoclusters were designed to tease out the effect of glycoligand presentation in carbohydrate recognition employing bacterial adhesion. The measured effects were rationalized by molecular modelling.
Citation for pulished version (APA): Chatterjee, K., Haushahn, B., Shen, C., Festersen, S., Waria... more Citation for pulished version (APA): Chatterjee, K., Haushahn, B., Shen, C., Festersen, S., Warias, J., Runge, B., ... Murphy, B. (2016). X-ray reflectivity investgation of structure and kinetics of photoswitchable lipid monolayers. Poster session presented at 80. Jahrestagung der DPG und DPG-Fruhjahrstagung, Regensburg, Germany.http://www.dpgverhandlungen.de/year/2016/conference/regensburg/part/bp/session/19
The Amadori Rearrangement as a Key Step to Inhibitors of Type 1-Fimbriated E. coli Bacteria
ACS Applied Materials & Interfaces, 2019
The synthesis of carbohydrate-functionalized thermosensitive poly(N-isoproylacrylamide) microgels... more The synthesis of carbohydrate-functionalized thermosensitive poly(N-isoproylacrylamide) microgels and their ability to bind carbohydrate-binding pathogens upon temperature switch is reported. It is found that the microgels' binding affinity is increased above their lower critical solution temperature (LCST) enabling thermo-triggerable capture of pathogens. Here a series of microgels with comparatively low mannose functionalization degrees below 1 mol % is achieved by a single polymerization step. Upon increase of mannose density, the microgel size increases and the LCST decreases to 26°C. Clustering with concanavalin A indicated that binding affinity is enhanced by a higher mannose content and by raising the temperature above the LCST. Binding studies with E. coli confirm stronger specific interactions above the LCST and formation of mechanically stable aggregates enabling efficient separation of E. coli by filtration. For small incubation times above LCST, the microgels' potential to release pathogens again below LCST is confirmed as well. Compared to existing switchable scaffolds, microgels nearly entirely composed of thermosensitive material undergo a large change in volume, which allows them to drastically vary the density of ligands to switch between capture and release. This is straightforward, yet novel approach is likely compatible with a broad range of bioactive ligands. Therefore, thermosensitive microgels represent a promising platform for the specific capture or release of cells or pathogens.
Sequence‐Defined Introduction of Hydrophobic Motifs and Effects in Lectin Binding of Precision Glycomacromolecules
Macromolecular Bioscience, 2019
This study investigates the influence of an increasingly hydrophobic backbone of multivalent glyc... more This study investigates the influence of an increasingly hydrophobic backbone of multivalent glycomimetics based on sequence‐defined oligo(amidoamines) on their resulting affinity toward bacterial lectins. Glycomacromolecules are obtained by stepwise assembly of tailor‐made building blocks on solid support, using both hydrophobic aliphatic and aromatic building blocks to enable a gradual change in hydrophobicity of the backbone. Their binding behavior toward model lectin Concanavalin A (ConA) is evaluated using isothermal titration calorimetry (ITC) and surface plasmon resonance (SPR) showing higher affinities for glycomacromolecules with higher content of hydrophobic and aromatic moieties in the backbone. Finally, glycomacromolecules are tested in a bacterial adhesion inhibition study against Escherichia coli where more hydrophobic backbones yield higher inhibitory potentials most likely due to additional secondary interactions with hydrophobic regions of the protein receptor as we...
Macromolecular Bioscience, 2017
A series of precision glycomacromolecules is prepared following previously established solid phas... more A series of precision glycomacromolecules is prepared following previously established solid phase synthesis allowing for controlled variations of interligand spacing and the overall number of carbohydrate ligands. In addition, now also different linkers are installed between the carbohydrate ligand and the macromolecular scaffold. The lectin binding behavior of these glycomacromolecules is then evaluated in isothermal titration calorimetry (ITC) and kinITC experiments using the lectin Concanavalin A (Con A) in its dimeric and tetrameric form. The results indicate that both sterical and statistical effects impact lectin binding of precision glycomacromolecules. Moreover, ITC results show that highest affinity toward Con A can be achieved with an ethyl phenyl linker, which parallels earlier findings with the bacterial lectin FimH. In this way, a first set of glycomacromolecule structures is selected for testing in a bacterial adhesion–inhibition study. Here, the findings point to a o...
Taking Responsibility for Society
ChemViews, 2017
En route from artificial to natural: Evaluation of inhibitors of mannose-specific adhesion of E. coli under flow
Biochimica et biophysica acta, 2016
We investigated the properties of six Escherichia coli adhesion inhibitors under static and under... more We investigated the properties of six Escherichia coli adhesion inhibitors under static and under flow conditions. On mannan-covered model substrates and under static conditions, all inhibitors were able to almost completely abolish lectin-mediated E. coli adhesion. On a monolayer of living human microvascular endothelial cells (HMEC-1), the inhibitors reduced adhesion under static conditions as well, but a large fraction of bacteria still managed to adhere even at highest inhibitor concentrations. In contrast, under flow conditions E. coli did not exhibit any adhesion to HMEC-1 not even at inhibitor concentrations where significant adhesion was detected under static conditions. This indicates that the presence of shear stress strongly affects inhibitor properties and must be taken into account when evaluating the potency of bacterial adhesion inhibitors.
Synthesis of AB4-type carbohydrate scaffolds as branching units in the glycosciences
Carbohydrate Research, 2016
Carbohydrate scaffolds, functionalised according to an AB4-type, were prepared on the basis of α-... more Carbohydrate scaffolds, functionalised according to an AB4-type, were prepared on the basis of α-d-mannopyranosides with various ethyl aglycone moieties, functionalised with 'A'. Four functional groups 'B' were installed at positions 2, 3, 4, and 6 of the sugar ring. In particular, we were interested in preparing N3(NH2)4-functionalised mannosides as multifunctional branching units for further orthogonal derivatisation or immobilisation on surfaces. A detailed synthetic study was performed which revealed that an azido function 'A' had to be installed at an advanced stage of the synthesis for successful preparation of the desired AB4-type carbohydrate scaffolds. The most successful synthetic sequence involved tetra-cyanoethylation of a 2-benzyloxyethyl mannopyranoside and subsequent reduction with in situ Boc protection to achieve (NHBoc)4 functionalisation. Finally, the benzyloxyethyl aglycon was converted into the corresponding azidoethyl moiety to gain access to the desired N3(NHBoc)4-functionalised carbohydrate scaffold. Its utilisation was exemplified by straightforward synthesis of a photosensitive glycoconjugate and a tetravalent glycocluster. Such compounds may be immobilised on functional surfaces to serve as tools in cell adhesion studies.
European Journal of Organic Chemistry, 2015
The study of bacterial adhesion is crucial to our understanding of infection processes as well as... more The study of bacterial adhesion is crucial to our understanding of infection processes as well as for the development of antiadhesives. Here we have investigated new nanodiamond glycoconjugates intended to inhibit adhesion of type 1 fimbriated E. coli bacteria. For conjugation of saccharides and nanodiamond, thiourea‐bridging was employed, a method that has not been used before in nanodiamond derivatization. Amino‐prefunctionalized diamond nanoparticles were prepared employing aromatic diazonium salts and reacted with different isothiocyanato‐functionalized mannose derivatives. The resulting glyconanodiamonds were characterized and then tested in bacterial binding assays. They are recognized by the bacterial protein FimH according to the structure‐activity relationships known for this lectin. Thus, owing to the particular properties of nanodiamond, a valuable material is introduced with the potential to control bacterial adhesion and colonization in a favorable way.
CHAPTER 1. Small Molecule Ligands for Bacterial Lectins: Letters of an Antiadhesive Glycopolymer Code
Polymer Chemistry Series, 2015
Microbial adhesion to surfaces is a suitable model to study mechanisms of cell adhesion. In addit... more Microbial adhesion to surfaces is a suitable model to study mechanisms of cell adhesion. In addition, it is a topic of medicinal relevance, as adhesion is often a prelude to infection. Microbial colonization is extensively connected to the glycome of the host organisms and thus to the glyocalyx nature of respective host cells. This relationship might be interpreted in analogy with the process of deciphering a code that is composed of sugars in this case. Bacteria use fimbriae, adhesive organelles projecting from the bacterial cell, to accomplish attachment to surfaces in a carbohydrate-specific manner. The highly virulent type 1 fimbriae of uropathogenic Escherichia coli (UPEC), for example, carry an α-d-mannoside-specific lectin called FimH, which is important for the adhesive process. Today, powerful small molecule FimH antagonists have been developed that raise the hope of developing an effective antiadhesion therapy against microbial infection. However, as adhesion factors are highly redundant and cell adhesion is very complex and multifaceted, new molecular architectures such as modern glycopolymers should be considered as additional tools in deciphering the glycocode. This chapter has been written to inspire some relevant ideas.
Mimicking Complex Carbohydrates to Inhibit Microbial Adhesion
XXIst International Carbohydrate Symposium 2002, 2002
Glycodendrimeric ligands of C-type lectin receptors as therapeutic agents in experimental cancer
Advances in Experimental Medicine and Biology, 2001
... in experimental cancer MILOSLAV POSPISIL, LUCA VANNUCCI*, ANNA FISEROVA, ICATHERINA KRAUSOVA,... more ... in experimental cancer MILOSLAV POSPISIL, LUCA VANNUCCI*, ANNA FISEROVA, ICATHERINA KRAUSOVA, ONDREJ HORVATH, VLADIMIR KREN, FRANCO MOSCA*, THISBE. ... A 7020006 of the Academy of Sciences of the Czech Republic and by ARPA Foundation-Pisa ...
50 Jahre Mitgliedschaft in der CG/GDCh - Wir gratulieren!
Nachrichten aus der Chemie, 2014
Im Jahre 2006 begehen die im folgenden genannten Kolleginnen und Kollegen das goldene Jubilaum ih... more Im Jahre 2006 begehen die im folgenden genannten Kolleginnen und Kollegen das goldene Jubilaum ihrer GDCh-Mitgliedschaft oder blicken in den neuen Bundeslandern auf eine 50 jahrige Mitgliedschaft in der Chemischen Gesellschaft der DDR und nach der Wiedervereinigung in der GDCh zuruck:
Glucose-Based AB2-Building Blocks for the Construction of Branched Glycopeptidomimetics
European Journal of Organic Chemistry, 2000
Glycopeptido derivatives are attractive oligosaccharide mimetics which allow the use of peptide-c... more Glycopeptido derivatives are attractive oligosaccharide mimetics which allow the use of peptide-coupling reactions for the assembly of carbohydrate units instead of the more difficult glycosylation procedures. Moreover, glycopeptidomimetics are attractive as synthetic ligands for carbohydrate-specific molecular recognition. With regard to the multiantennary nature of the naturally occurring N-glycans, we synthesized the orthogonally protected glucose-based AB2-building blocks 1 and 2, which allow the assembly of branched glycopeptidomimetics by peptide-coupling reactions. This was exemplified by the synthesis of multivalent glycopeptidomimetics 14 and 15 derived therefrom.
Chemie in unserer Zeit, 2017
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Papers by Thisbe Lindhorst