Trivalent α-D-mannoside clusters as inhibitors of type-1 fimbriae-mediated adhesion of Escherichia coli: structural variation and biotinylation

Lindhorst, Thisbe K.; Kötter, Sven; Krallmann-Wenzel, Ulrike; Ehlers, Stefan

doi:10.1039/b009786l

Cited by 74 publications

(68 citation statements)

References 28 publications

(17 reference statements)

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“…On the other hand, the importance of the nature of the scaffolding unit for the affinity of clustered mannosides was also revealed. Four clusters with ethylene glycol (EG) spa-cers were tested (Table 1): trivalent clusters 32 and 33, [53] both yielding a high RIP of 1063, and tetravalent molecules 34 and 35, [54] which had a 100 times lower RIP in the same assay system. Thus, in spite of the fact that the same type of linkers were used for clustering in all four cases, their inhibitory behaviour differed significantly.…”

Section: Multivalent Glycomimetics As Inhibitors Of Type 1 Fimbriae-mmentioning

confidence: 99%

“…To be able to compare two such ELISA measurements with one another, a standard inhibitor has to be tested on the same test plate, so that the poorly comparable IC 50 values from different experiments can be uniformly referenced. Different ELISA experiments have been performed by using whole E. coli cells, [26,44,48,[51][52][53][54]61,62,[74][75][76] type 1 fimbriae [77] and the isolated FimCH protein complex. [78] Assays similar to the ELISA method have been developed.…”

Section: Assays On Surfacesmentioning

confidence: 99%

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The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

2011

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Adhesion is a prerequisite for bacteria to colonize cell surfaces. To accomplish cellular adhesion, many bacteria use carbohydrate‐specific lectins, which are expressed as part of capillary protein appendages expanding from their surface, called fimbriae or pili. For bacteria, colonization of cell surfaces offers advantageous conditions to persist and multiply. For the host, however, bacterial colonization can be affiliated with severe health problems such as inflammation. Therefore, to combat bacterial adhesion and inflammatory diseases, investigation of the molecular and biophysical details of the relevant lectin–carbohydrate interactions is important. Understanding molecular carbohydrate recognition can lead to the development of high‐affinity inhibitors of bacterial lectins. That way, interfering with the bacterial attachment to surfaces proves the vision of an antiadhesion therapy, among others, against uropathogenic E. coli (UPEC). One of the most important and best investigated bacterial lectins is the mannose‐specific protein FimH, which is expressed on the tips of type 1 fimbriae. During the last 30 years, many natural as well as synthetic mannosidic ligands of FimH have been designed and tested for their inhibitory potencies. We report key results and comment on key problems and perspectives of this research.

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Section: Multivalent Glycomimetics As Inhibitors Of Type 1 Fimbriae-mmentioning

confidence: 99%

Section: Assays On Surfacesmentioning

confidence: 99%

The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

2011

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“…The aminoethyl monosaccharide 27 was synthesized in three steps from the commercial peracetylated mannose: standard glycosylation with 2-N-Z-ethanolamine in the presence of BF 3 ·Et 2 O, deacetylation, followed by hydrogenation of the benzyloxycarbonyl group [46] (see the Supporting Information). The aminoethyl mannosides 28 and 29 were obtained by glycosidation of thiotolyl di-and trimannoside donors, prepared by Wongs one-pot self-condensation strategy,…”

Section: Preparation Of Neoglycoconjugates By Peptidic Couplingmentioning

confidence: 99%

Gold Manno‐Glyconanoparticles: Multivalent Systems to Block HIV‐1 gp120 Binding to the Lectin DC‐SIGN

Martinez-Avila

Hijazi

Marradi

et al. 2009

Chemistry A European J

174

179

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The HIV envelope glycoprotein gp120 takes advantage of the high-mannose clusters on its surface to target the C-type lectin dendritic cell-specific intracellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) on dendritic cells. Mimicking the cluster presentation of oligomannosides on the virus surface is a strategy for designing carbohydrate-based antiviral agents. Bio-inspired by the cluster presentation of gp120, we have designed and prepared a small library of multivalent water-soluble gold glyconanoparticles (manno-GNPs) presenting truncated (oligo)mannosides of the high-mannose undecasaccharide Man(9)GlcNAc(2) and have tested them as inhibitors of DC-SIGN binding to gp120. These glyconanoparticles are ligands for DC-SIGN, which also interacts in the early steps of infection with a large number of pathogens through specific recognition of associated glycans. (Oligo)mannosides endowed with different spacers ending in thiol groups, which enable attachment of the glycoconjugates to the gold surface, have been prepared. manno-GNPs with different spacers and variable density of mannose (oligo)saccharides have been obtained and characterized. Surface plasmon resonance (SPR) experiments with selected manno-GNPs have been performed to study their inhibition potency towards DC-SIGN binding to gp120. The tested manno-GNPs completely inhibit the binding from the micro- to the nanomolar range, while the corresponding monovalent mannosides require millimolar concentrations. manno-GNPs containing the disaccharide Manalpha1-2Manalpha are the best inhibitors, showing more than 20 000-fold increased activity (100 % inhibition at 115 nM) compared to the corresponding monomeric disaccharide (100 % inhibition at 2.2 mM). Furthermore, increasing the density of dimannoside on the gold platform from 50 to 100 % does not improve the level of inhibition.

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“…The Dowex M-4195 resin was purchased from Supelco and subjected to a conditioning treatment. The vinyl sulfone propyl silica gel 5, [28] the aminopropyl silica gel 6, [29] the alkynes 10, [38] 15, [39] 16, [40] 17, [41] 18 [42] and 19, [43] the azides 21, [44] 22, [45] 23, [46] 24, [47] 25, [48] 27, [49] and 28 [50] and the alkyne and azido functionalized silicas [33] used as click scavengers were prepared according to reported procedures in literature. TLCs were performed on Merck Silica Gel 60 F 254 aluminium sheets.…”

Section: Experimental Section Generalmentioning

confidence: 99%

Non‐Magnetic and Magnetic Supported Copper(I) Chelating Adsorbents as Efficient Heterogeneous Catalysts and Copper Scavengers for Click Chemistry

et al. 2010

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Novel supported chelating adsorbents bearing diverse multidentate nitrogenated ligands with strong copper(I) affinities are easily prepared in non-magnetic and magnetic variants using silica and silica-coated magnetite nanoparticles as suitable supports and the aza-Michael-type addition of vinyl sulfones as the ligation tool. These adsorbents are versatile materials with applications in the copper-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry where their complexation abilities enable them to act either as heterogeneous click catalysts when used in their complexed form or as copper(I) scavengers when used in their uncomplexed form. In the first instance, they proved to be robust and efficient heterogeneous catalysts to promote click reactions using extremely low doses and showing negligible copper leaching, particularly in the case of the silica-based non-magnetic adsorbents, allowing a simple operational protocol for their rapid and easy removal by filtration or magnetic decantation and showing good recyclability properties. In their uncomplexed form, the non-magnetic chelating adsorbents are very efficient copper scavengers that are able to remove any traces of metal contamination and that can be applied in tandem with any heterogeneous supported copper(I) catalysts or as standalone copper removing system in any click protocol allowing the isolation of metal-free clicked compounds.

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Trivalent α-D-mannoside clusters as inhibitors of type-1 fimbriae-mediated adhesion of Escherichia coli: structural variation and biotinylation

Cited by 74 publications

References 28 publications

The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

Gold Manno‐Glyconanoparticles: Multivalent Systems to Block HIV‐1 gp120 Binding to the Lectin DC‐SIGN

Non‐Magnetic and Magnetic Supported Copper(I) Chelating Adsorbents as Efficient Heterogeneous Catalysts and Copper Scavengers for Click Chemistry

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