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Search for "FimH" in Full Text gives 12 result(s) in Beilstein Journal of Organic Chemistry.
Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA
Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132
- the bacteria. Bacterial lectins are therefore attractive targets for the development of new antibiotic-sparing anti-infective drugs. For example, some Escherichia coli fimbrial lectin FimH inhibitors are currently in clinical development to treat and prevent urinary tract infections [9][10]. A large
- [11][12][13][14][15][16][17][18]. The group of Lindhorst has reported a series of mannosyl azobenzenes targeting E. coli lectin FimH, demonstrating the possibility to control the type 1 fimbriae-mediated bacterial adhesion to a self-assembled monolayer of mannosyl azobenzene on a gold surface [19][20
Lectins of Mycobacterium tuberculosis – rarely studied proteins
Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1
- bacterial lectins are the mannose-specific FimH of type 1 fimbriae and the galabiose-specific PapG of P fimbriae, expressed by Enterobactericea, such as Escherichia coli (E. coli). While type 1-fimbrial expression of E. coli is associated with urinary tract infections, the presence of P fimbriae is
- , which act as FimH antagonists, for example, have been successfully used to significantly reduce the severity of E. coli infections of the urinary tract in mice [66]. Furthermore, preliminary clinical trials with D-mannose indicate promising effects of this monosaccharide on controlling urinary tract
- results are similar to previous observations with other lectins. Adhesion and inhibition studies with the fimbrial lectin FimH of E. coli bacteria, for example, also revealed higher affinities of glycosides carrying an aromatic aglycon compared to derivatives with aliphatic aglycon portions. This finding
Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections
Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239
- and invade bladder and kidney tissue, and to promote biofilm formation. Bladder-adhesive FimH is a mannose-specific lectin and the kidney-adhesive PapG binds galactosides. In a second indication, FimH also mediates the attachment of E. coli to the gut, inducing inflammation in Crohn’s disease [13
- ]. The crystal structure of FimH was published by Hultgren and Knight et al. in 1999 [14]. FimH is highly specific for α-D-mannoside ligands with this residue residing in a carbohydrate binding pocket with its α-linked substituent towards an adjacent cleft. This substituent, termed the aglycon, can also
- aglycon part of the mannosides. The attachment of lipophilic aglycons to an α-linked mannose residue was identified to increase the binding potency tremendously due to the opening of a lipophilic cleft on FimH, the tyrosine gate [15]. Various alkyl mannosides 1 (Figure 1) were analyzed and n-heptyl
Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH
Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163
- ligand–receptor interactions in solution. We have employed an interdisciplinary methodology to achieve facile photolabeling of the lectin FimH, which is a bacterial protein, crucial for adhesion, colonization and infection. Following our earlier work, we have here designed and synthesized diazirine
- -functionalized mannosides as high-affinity FimH ligands and performed an extensive study on photo-crosslinking of the best ligand (mannoside 3) with a series of model peptides and FimH. Notably, we have employed high-performance mass spectrometry to be able to detect radiation results with the highest possible
- accuracy. We are concluding from this study that photolabeling of FimH with sugar diazirines has only very limited success and cannot be regarded a facile approach for covalent modification of FimH. Keywords: diazirines; docking; FimH; lectin ligands; mannosides; mass spectrometry; photoaffinity labelling
What contributes to an effective mannose recognition domain?
Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255
- mammalian mannose-binding sites are in general flat and solvent exposed, the half-lives of carbohydrate–lectin complexes are rather short since water molecules can easily access and displace the ligand from the binding site. In contrast, the bacterial lectin FimH benefits from a deep mannose-binding site
- , leading to a substantial improvement in the off-rate. Together with both a catch-bond mechanism (i.e., improvement of affinity under shear stress) and multivalency, two methods commonly utilized by pathogens, the affinity of the carbohydrate–FimH interaction can be further improved. Including those just
- lectin LecB [29][30] and Burkholderia cenocepacia with its characteristic B. cenocepacia lectin A (BC2L-A) [31][32], both playing an important role in the social life of bacterial cells. A further example is the bacterial adhesin FimH, which plays a crucial role in urinary tract infections (UTIs). FimH
Glyco-gold nanoparticles: synthesis and applications
Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100
- , on the base of different expression level of the bacterial lectin FimH with a colorimetric assay. A simple and fast bioassay has been developed by Lee et al. [83] to recognize cholera toxin (CT), a protein secreted by the Vibrio cholerae bacterium which is responsible for cholera disease. A thiol
Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?
Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123
- site of the type 1-fimbrial lectin FimH. Keywords: Amadori rearrangement; bacterial adhesion; C-mannosides; docking studies; FimH ligands; Introduction The Amadori rearrangement (AR) is the reaction in which aldohexoses react with suitable amines under acidic catalysis to 1-amino-1-deoxyketohexoses
- investigation of ligands for the bacterial lectin FimH [4] it has been our goal to investigate the Amadori rearrangement as a method to approach new FimH ligands. These are especially relevant in the context of an anti-adhesion therapy against bacterial infections [5][6]. As FimH-mediated adhesion to the
- glycosylated surface of host cells is a key step in infections caused by type 1-fimbriated bacteria, FimH antagonists that inhibit bacterial adhesion can be valuable for treatment of infectious diseases [7][8]. The structure of type 1-fimbrial lectin FimH has been elucidated in X-ray analysis [9][10][11
Synthesis and testing of the first azobenzene mannobioside as photoswitchable ligand for the bacterial lectin FimH
Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26
- adhesive surfaces. Keywords: azobenzene glycosides; bacterial adhesion; E/Z photoisomerisation; FimH antagonists; mannobiosides; molecular switches; sweet switches; Introduction Adhesion of bacteria to surfaces can be a severe problem both in vivo and in vitro. Hence, inhibition of bacterial adhesion by
- -mannosyl-specific lectin FimH at the tip of the fimbrial shaft. FimH antagonists are currently considered as new therapeutics for the treatment of urinary tract infections [6]. The carbohydrate specificity of FimH has been investigated in great detail [7] and its structure is well-known from several X-ray
- studies [8][9][10][11]. It has turned out that the 1,3-linked mannobioside α-D-Man-(1→3)-D-Man (1, Figure 1B) is an ideal disaccharide ligand for FimH [3][12]. All other isomeric mannobiosides do not bind favourably to FimH. Therefore, we have designed the respective azobenzene mannobioside 2 (Figure 1C
Synthetic glycopeptides and glycoproteins with applications in biological research
Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90
- monosaccharide ligands have been prepared and evaluated [123]. The type 1 fimbriated Echerichia coli is a pathogen responsible for urinary tract infections with millions of cases every year [124]. The type 1 fimbriae have been identified to be a major contributor to these infections [125][126]. The FimH lectin
- on type 1 fimbriae is an attractive target for the inhibition of α-mannose-mediated cell adhesion [127][128][129][130][131]. Previous X-ray studies have proven that the FimH lectin has a monovalent binding site recognizing α-D-mannose [132][133]. In close proximity to the mannose-binding crevice, two
- tyrosine residues form the “tyrosine gate” [134]. By π–π stacking interactions with the aromatic tyrosine residues, monovalent α-mannose ligands containing hydrophobic aglycons, have shown increased binding affinities [128][135][136]. Employing multivalent ligands, the binding affinity to FimH could be
Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS
Beilstein J. Org. Chem. 2012, 8, 753–762, doi:10.3762/bjoc.8.86
- be useful in a bacterial adhesion inhibition assay against the bacterial lectin FimH [20][21]. The second glycoside 7 has been used previously for well-established enzymatic surface modifications [22]. Both these compounds can be synthesised by starting from commercially available 11
En route to photoaffinity labeling of the bacterial lectin FimH
Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91
- , Uppsala Biomedical Center, SE-75124 Uppsala, Sweden 10.3762/bjoc.6.91 Abstract Mannose-specific adhesion of Escherichia coli bacteria to cell surfaces, the cause of various infections, is mediated by a fimbrial lectin, called FimH. X-ray studies have revealed a carbohydrate recognition domain (CRD) on
- FimH that can complex α-D-mannosides. However, as the precise nature of the ligand–receptor interactions in mannose-specific adhesion is not yet fully understood, it is of interest to identify carbohydrate recognition domains on the fimbrial lectin also in solution. Photoaffinity labeling serves as an
- appropriate methodology in this endeavour and hence biotin-labeled photoactive mannosides were designed and synthesized for photoaffinity labeling of FimH. So far, the photo-crosslinking properties of the new photoactive mannosides could be detailed with the peptide angiotensin II and labeling of FimH was
A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH
Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90
- Thisbe K. Lindhorst Kathrin Bruegge Andreas Fuchs Oliver Sperling Christiana Albertina University of Kiel, Otto Diels Institute of Organic Chemistry, Otto-Hahn-Platz 4, D-24098 Kiel, Germany, Fax: +49 431 8807410 10.3762/bjoc.6.90 Abstract FimH is a mannose-specific bacterial lectin found on type
- capacity to bridge two putative carbohydrate binding sites on FimH was designed and synthesized. Anti-adhesion assays with the new bivalent ligand and type 1-fimbriated bacteria have revealed, that verification of the number of carbohydrate binding sites on FimH with a tailor-made bivalent glycopeptide
- requires further investigation to be conclusive. Keywords: bacterial adhesion; bivalent ligand; ELISA; FimH; glycopeptides; Introduction Bacterial adhesion is a phenomenon which occurs on the surface of host cells as well as on the surface of surgical implants, where it can lead to the formation of
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