Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• interactions strongly contribute to bacterial adhesion and uptake, and are also associated with the capability of Mtb to survive, replicate, and persist within macrophages [21][22][23][24][25]. Ubiquitous in both eukaryotes and prokaryotes, lectins comprise a subclass of glycan-binding proteins most commonly

• bacterial agglutination have provided initial insights into carbohydrate specificity, sub-cellular location and functions of putative mycobacterial lectins. In the thesis of K. Kolbe various sugar derivatives were immobilized in 96 well microtiter plates via an amino group. Bacterial adhesion was studied

• express lectins on the cell surface (e.g., dendritic cell-specific C-type lectins (Dectin), the macrophage inducible C-type lectin (Mincle), the macrophage C-type lectin (MCL), and the mannose receptor (MR)), which recognize carbohydrates of the Mtb cell wall. These proteins contribute to bacterial

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• pathogen [10]. 3. Blocking adhesion and biofilm formation Bacterial adhesion to the host’s tissue is the initial step of every infection. In many cases, microbial adhesion is mediated by carbohydrate-binding proteins, so-called lectins, which recognize glycoconjugates on the surface of cells and tissue

• , Titz et al. have developed small molecule LecB inhibitors derived from mannose and obtained potent monovalent inhibitors (compound 15) of LecB-mediated bacterial adhesion [47]. The sulfonamide 15 and cinnamide 16 were developed to take advantage of interactions with a nearby shallow pocket, and indeed

• potential (RIP), which is benchmarked with the reference methyl α-D-mannoside (1a) defined as RIP = 1, was increased up to 6900-fold [17]. The biphenyl mannosides (e.g., 4, 5) have subsequently been identified by the Ernst and Hultgren/Janetka groups as promising inhibitors of FimH-mediated bacterial

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• carbohydrate binding site. A more negative value predicts better binding. Scores obtained for mannosides 3 and 4 suggest a high affinity for FimH, surpassing that of pNPMan 1 for both protein conformations tested (Table 1). (Diazirines cannot be tested in bacterial adhesion–inhibition assays due to their light

• standard method for FimH labeling. As we wish to eventually control bacterial adhesion by crosslinking of functional molecules to the adhesin (FimH), we will in the future utilize alternative labeling chemistry to efficiently target FimH. Experimental Peptides and proteins For photolabeling experiments

What contributes to an effective mannose recognition domain?

• Christoph P. Sager,
• Deniz Eriş,
• Martin Smieško,
• Rachel Hevey and
• Beat Ernst

Beilstein J. Org. Chem. 2017, 13, 2584–2595, doi:10.3762/bjoc.13.255

• carbohydrate–lectin interactions of the innate immune system but also in bacterial adhesion, a process key for the bacterium’s survival. In an effort to better understand the particular characteristics, which contribute to a successful carbohydrate recognition domain, the mannose-binding sites of six C-type

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• different bacterial adhesion. Indeed, gold nanorods presented a bacteria detection limit of 0.03 ± 0.01 µg/mL, 80-folds more sensitive than spherical and star shaped AuNPs. This discrepancy has been ascribed to the difference in the relative amount of mannose involved in the NP-bacteria interaction. The

Are D-manno-configured Amadori products ligands of the bacterial lectin FimH?

• Tobias-Elias Gloe,
• Insa Stamer,
• Cornelia Hojnik,
• Tanja M. Wrodnigg and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 1096–1104, doi:10.3762/bjoc.11.123

• E. coli bacteria by means of molecular docking and bacterial adhesion studies. It turns out that Amadori rearrangement products have a limited activity as inhibitors of bacterial adhesion because the β-C-glycosidically linked aglycone considerably hampers complexation within the carbohydrate binding

• 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

• 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

• Vijayanand Chandrasekaran,
• Katharina Kolbe,
• Femke Beiroth and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2013, 9, 223–233, doi:10.3762/bjoc.9.26

• control of carbohydrate-specific bacterial adhesion, it has become our goal to synthesise azobenzene mannosides as photoswitchable inhibitors of type 1 fimbriae-mediated adhesion of E. coli. An azobenzene mannobioside 2 was prepared and its photochromic properties were investigated. The E→Z isomerisation

• was found to be highly effective, yielding a long-lived (Z)-isomer. Both isomers, E and Z, show excellent water solubility and were tested as inhibitors of mannoside-specific bacterial adhesion in solution. Their inhibitory potency was found to be equal and almost two orders of magnitude higher than

• 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

Efficient synthesis of phenylene-ethynylene rods and their use as rigid spacers in divalent inhibitors

• Francesca Pertici,
• Norbert Varga,
• Arnoud van Duijn,
• Matias Rey-Carrizo,
• Anna Bernardi and
• Roland J. Pieters

Beilstein J. Org. Chem. 2013, 9, 215–222, doi:10.3762/bjoc.9.25

• obtained after deprotection of the alkyne moieties with K2CO3. Preliminary application As part of our program on bacterial adhesion inhibition by multivalent carbohydrates, the bacterial lectin LecA, a virulence factor of the problematic pathogen Pseudomonas aeruginosa is a target of interest [30][31

Formation of carbohydrate-functionalised polystyrene and glass slides and their analysis by MALDI-TOF MS

• Martin J. Weissenborn,
• Johannes W. Wehner,
• Christopher J. Gray,
• Robert Šardzík,
• Claire E. Eyers,
• Thisbe K. Lindhorst and
• Sabine L. Flitsch

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

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• -mannoside (pNPMan), respectively (Table 1). When these mannosides were tested as inhibitors of type 1 fimbriae-mediated bacterial adhesion to a mannan-coated surface in an ELISA [21][22], IC50-values were obtained, which reflect the concentration of the derivative employed, that leads to 50% inhibition of

• bacterial adhesion. Three independent measurements resulted in high standard deviations, a typical characteristic of this assay, whereas the relative trend in a series of tested ligands can be verified with high reproducibility. Hence, the inhibitory potencies of the tested ligands were referenced to an

A bivalent glycopeptide to target two putative carbohydrate binding sites on FimH

• Thisbe K. Lindhorst,
• Kathrin Bruegge,
• Andreas Fuchs and
• Oliver Sperling

Beilstein J. Org. Chem. 2010, 6, 801–809, doi:10.3762/bjoc.6.90

• 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

• persistent biofilms. In all cases of bacterial adhesion and of biofilm formation severe health problems can result for the host organism [1][2]. A number of microbial adhesins are known, that co-operate in the adhesion process [3], such as the fimbriae, which are long filamentous adhesive organells on the

• -mediated bacterial adhesion The synthesis of the bivalent glycopeptide 1 was not optimized in order to improve all the individual yields, because it has been the primary goal of this study to test the anti-adhesive properties of this type of ligand. An ELISA was performed as reported earlier [32][33

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

•  1). They are considered to play a major role in immuno defense against bacterial and viral infections in the gastrointestinal tract of infants [5]. It is thought that they effectively inhibit bacterial adhesion to epithelial surfaces and so block the first stages of infection processes. Thus, these