Mirja Hartmann
University of Kiel
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Publication
Featured researches published by Mirja Hartmann.
ChemBioChem | 2011
Carsten Grabosch; Mirja Hartmann; Jörn Schmidt-Lassen; Thisbe K. Lindhorst
Bacteria use long proteinaceous appendages, called fimbriae or pili, to adhere to the surfaces of their host cells. Widely distributed among the Enterobacteriacae are type 1 fimbriae that mediate mannose‐specific bacterial adhesion through the lectin FimH, located at the fimbrial tips. It is possible to design synthetic mannosides such that they show high affinity for FimH and can thus inhibit mannose‐specific bacterial adhesion in a competitive manner. It has been found that mannosidic squaric acid monoamides serve especially well as inhibitors of type 1 fimbriae‐mediated bacterial adhesion, but it has remained unclear whether this effect is due to specific inhibition of the bacterial lectin FimH or to unspecific bioconjugation between the lectins carbohydrate binding site and a squaric acid monoamide. A bioconjugation reaction would result in a covalently crosslinked squaric acid diamide. Here it is shown that covalent inhibition of FimH by mannosidic squaric acid derivatives is very unlikely and that compounds of this type serve rather as excellent specific candidates for low‐molecular‐weight inhibitors of bacterial adhesion. This has been verified by testing the properties of glycosidic squaric acid monoamides in diamide formation, by two different adhesion assays with a series of selected control compounds, and by molecular docking studies that further support the results obtained in the bioassays.
FEBS Letters | 2012
Mirja Hartmann; Heike Papavlassopoulos; Vijayanand Chandrasekaran; Carsten Grabosch; Femke Beiroth; Thisbe K. Lindhorst; Claudia Röhl
Bacterial adhesion to glycosylated surfaces is a key issue in human health and disease. Inhibition of bacterial adhesion by suitable carbohydrates could lead to an anti‐adhesion therapy as a novel approach against bacterial infections. A selection of five α‐mannosides has been evaluated as inhibitors of bacterial adhesion to the polysaccharide mannan, as well as to the surface of live human HT‐29 cells. Cell toxicity studies were performed to identify the therapeutic window for a potential in vivo‐application of the tested carbohydrates. A previously published mannosidic squaric acid diamide was shown to be exceptionally effective as inhibitor of the bacterial lectin FimH.
Carbohydrate Research | 2013
Johannes W. Wehner; Mirja Hartmann; Thisbe K. Lindhorst
Bacterial adhesion to the glycocalyx of human host cells is of biological and medicinal importance. This process is often initiated by the interaction of bacterial lectins and specific carbohydrate ligands. Thus, adhesion of bacterial cells to glycosylated surfaces is a suitable model system to study various parameters of lectin-mediated carbohydrate recognition. Glycoarrays have become important tools to study such lectin-mediated carbohydrate recognition. However, it is difficult to adjust the characteristics of a specific glycoarray regarding its carbohydrate density or the clustering of sugar ligands, respectively. Thus, we have made an attempt to use synthetic cluster glycosides of different valencies to vary carbohydrate density on a polystyrene surface. A series of mono-, di- and trivalent mannosides were synthesised for immobilisation on pre-functionalised polystyrene microtiter plates and the resulting glycoarrays were tested as adhesive surfaces in mannose-specific adhesion of Escherichia coli. Our measurements give first promising hints about the potential of this approach to alter ligand density of glycoarrays in a systematic way.
Carbohydrate Research | 2011
Alexander Schierholt; Mirja Hartmann; Thisbe K. Lindhorst
In order to test relevant structural parameters for effective inhibition of mannose-specific bacterial adhesion, bi- and trivalent glycopeptide α-D-mannopyranosides were synthesized that differ in their conformational properties as well as in the spatial arrangement of attached mannosyl residues. They were tested in an inhibition adhesion assay with fluorescent Escherichia coli bacteria and testing results were referenced to the inhibitory potency of methyl α-D-mannopyranoside. It was shown, that besides the nature of the mannoside aglycon moiety, scaffolding of α-D-mannopyranosides on a peptide backbone was important for the performance of the synthesized glycopeptides as inhibitors of bacterial adhesion.
Organic and Biomolecular Chemistry | 2012
Johannes W. Wehner; Martin J. Weissenborn; Mirja Hartmann; Christopher J. Gray; Robert Šardzík; Claire E. Eyers; Sabine L. Flitsch; Thisbe K. Lindhorst
There is a wide range of immobilisation reactions to tether substrates to a variety of surfaces for array-based analysis. Most of these immobilisation strategies are specific for a particular surface and require an additional linker to be attached to the substrate or the surface. Furthermore, the analysis of functionalised surfaces is often restricted to certain analytical techniques and therefore, different immobilisation strategies for different surfaces are desirable. Here we have tested an S-tritylated linker for non-covalent or covalent immobilisation of mannosides to polystyrene or gold surfaces. S-Tritylated mannosides with varying linkers were readily synthesised and used to add to biorepulsive maleimide-terminated preformed SAMs after in situ deprotection of the S-trityl group. In addition, S-tritylated mannosides themselves formed stable glycoarrays on polystyrene microtiter plates. The glycoarrays were successfully analysed by MALDI-ToF mass spectrometry, SPR spectroscopy, and interrogated with GFP-transfected Escherichia coli cells. This work has shown that a dual purpose linker can be used on multiple surfaces to form arrays allowing for different testing as well as analytical approaches.
Analytical Chemistry | 2017
Christopher J. Gray; Antonio Sánchez-Ruíz; Ivana Šardzíková; Yassir Ahmed; Rebecca L. Miller; Juana Elizabeth Reyes Martínez; Edward Pallister; Kun Huang; Peter Both; Mirja Hartmann; Hannah N. Roberts; Robert Šardzík; Santanu Mandal; Jerry Turnbull; Claire E. Eyers; Sabine L. Flitsch
The identification of carbohydrate-protein interactions is central to our understanding of the roles of cell-surface carbohydrates (the glycocalyx), fundamental for cell-recognition events. Therefore, there is a need for fast high-throughput biochemical tools to capture the complexity of these biological interactions. Here, we describe a rapid method for qualitative label-free detection of carbohydrate-protein interactions on arrays of simple synthetic glycans, more complex natural glycosaminoglycans (GAG), and lectins/carbohydrate binding proteins using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The platform can unequivocally identify proteins that are captured from either purified or complex sample mixtures, including biofluids. Identification of proteins bound to the functionalized array is achieved by analyzing either the intact protein mass or, after on-chip proteolytic digestion, the peptide mass fingerprint and/or tandem mass spectrometry of selected peptides, which can yield highly diagnostic sequence information. The platform described here should be a valuable addition to the limited analytical toolbox that is currently available for glycomics.
European Journal of Organic Chemistry | 2011
Mirja Hartmann; Thisbe K. Lindhorst
Chemical Communications | 2010
Mirja Hartmann; Andrea Kristina Horst; Per Klemm; Thisbe K. Lindhorst
European Journal of Organic Chemistry | 2010
Alexander Schierholt; Mirja Hartmann; Kirsten Schwekendiek; Thisbe K. Lindhorst
European Journal of Organic Chemistry | 2009
Sara Spjut; Maciej Pudelko; Mirja Hartmann; Mikael Elofsson