Nonhydrolyzable C-disaccharides, a new class of DC-SIGN ligands

Bertolotti, Benedetta; Oroszová, Beáta; Sutkevičiūtė, Ieva; Kniežo, L.; Fieschi, Franck; Parkan, Kamil; Lövyova, Zuzana; Kašáková, Martina; Moravcová, Jitka

doi:10.1016/j.carres.2016.09.005

Cited by 15 publications

(25 citation statements)

References 51 publications

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“…21 The only modification in regard to the published approach was the first step where the 2-(2,3,4,6-tetra-Oacetyl-α-D-mannopyranosyl)prop-1-ene was obtained from methyl α-D-mannopyranoside using silylation-reductive cleavagedeprotection strategy 22 adapted for the manno configuration. 18 The alcohol 8 was converted to the azide 9 by a direct azidation as described above in 84% yield. The final Zemplén´s deacetylation of both 7 and 9 produced unprotected azides 2 and 1, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Secondly, biological tests carried out with our monovalent and divalent Cglycosidic ligands were completed indicating L-fuco configuration as more active ligand in comparison with D-manno configuration. 18 Moreover, very minor affinity improvement of tetra-and hexavalent dendrimers based on the O-mannopyranosylated scaffold was found. 16 In this context, a full series of L-fuco dendrimers carrying 4, 6, 9, and 12 units were prepared whilst only two constructs with 9 and 12 D-manno units attached were made.…”

Section: Resultsmentioning

confidence: 99%

“…28 The reference monosaccharides D-mannose and L-fucose were found to exhibit IC50 values of 3.39 and 2.06 mM respectively which are consistent with our previous results. 18,25,26 Initially the affinity of azides 1 and 2 was tested in order to check if the affinity of Cglycosides could be comparable with those of the parent hexoses.…”

Section: Resultsmentioning

confidence: 99%

“…17 Recently we have demonstrated for the first time that divalent C-disaccharides based on D-mannose or L-fucose scaffold can be prospective ligands for the DC-SIGN receptor. 18 To verify if Cpseudoglycosides are adequate candidates for the construction of multivalent systems, we present here a new class of potentially stable pseudoglycodendrimers with different valences. The affinities of these constructs for DC-SIGN were evaluated by SPR competition assays and compared with their parent O-glycosidic dendrimers.…”

Section: Introductionmentioning

confidence: 99%

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Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

et al. 2017

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The C-type lectin DC-SIGN expressed on immature dendritic cells is a promising target for antiviral drug development. Previously, we have demonstrated that mono- and divalent C-glycosides based on d-manno and l-fuco configurations are promising DC-SIGN ligands. Here, we described the convergent synthesis of C-glycoside dendrimers decorated with 4, 6, 9, and 12 α-l-fucopyranosyl units and with 9 and 12 α-d-mannopyranosyl units. Their affinity against DC-SIGN was assessed by surface plasmon resonance (SPR) assays. For comparison, parent O-glycosidic dendrimers were synthesized and tested, as well. A clear increase of both affinity and multivalency effect was observed for C-glycomimetics of both types (mannose and fucose). However, when dodecavalent C-glycosidic dendrimers were compared, there was no difference in affinity regarding the sugar unit (l-fuco, IC 17 μM; d-manno, IC 12 μM). For the rest of glycodendrimers with l-fucose or d-mannose attached by the O- or C-glycosidic linkage, C-glycosidic dendrimers were significantly more active. These results show that in addition to the expected physiological stability, the biological activity of C-glycoside mimetics is higher in comparison to the corresponding O-glycosides and therefore these glycomimetic multivalent systems represent potentially promising candidates for targeting DC-SIGN.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

et al. 2017

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“…Therefore, pseudo- C -disaccharides 2 – 4 23 as monovalent ligands differing in the structure of the C -aglycone part were included in the study to analyse the potential influence of the second saccharide-like unit on the ligand binding. 1,4-bis(fucopyranosyl)butane 5 23 is a divalent mimetic in which the distance between the C1 atoms of both α- l -fucopyranosyl units is derived from the structure of blood group Lewis b tetrasaccharide. Tetravalent constructs 6 and 7 contain a calix[4]arene scaffold in a 1,3- alternate conformation that ensures sufficient solubility in water.…”

Section: Resultsmentioning

confidence: 99%

Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica

Paulíková

Houser

Kašáková

et al. 2019

Sci Rep

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A recently described bangle lectin (PHL) from the bacterium Photorhabdus asymbiotica was identified as a mainly fucose-binding protein that could play an important role in the host-pathogen interaction and in the modulation of host immune response. Structural studies showed that PHL is a homo-dimer that contains up to seven l-fucose-specific binding sites per monomer. For these reasons, potential ligands of the PHL lectin: α-l-fucopyranosyl-containing mono-, di-, tetra-, hexa- and dodecavalent ligands were tested. Two types of polyvalent structures were investigated – calix[4]arenes and dendrimers. The shared feature of all these structures was a C-glycosidic bond instead of the more common but physiologically unstable O-glycosidic bond. The inhibition potential of the tested structures was assessed using different techniques – hemagglutination, surface plasmon resonance, isothermal titration calorimetry, and cell cross-linking. All the ligands proved to be better than free l-fucose. The most active hexavalent dendrimer exhibited affinity three orders of magnitude higher than that of standard l-fucose. To determine the binding mode of some ligands, crystal complex PHL/fucosides 2 – 4 were prepared and studied using X-ray crystallography. The electron density in complexes proved the presence of the compounds in 6 out of 7 fucose-binding sites.

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Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

et al. 2020

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Carbohydrates play a pivotal role in intercellular communication processes. In particular, glycan antigens are key for sustaining homeostasis, helping leukocytes to distinguish damaged tissues and invading pathogens from healthy tissues. From a structural perspective, this cross-talk is fairly complex, and multiple membrane proteins guide these recognition processes, including lectins and Toll-like receptors. Since the beginning of this century, lectins have become potential targets for therapeutics for controlling and/or avoiding the progression of pathologies derived from an incorrect immune outcome, including infectious processes, cancer, or autoimmune diseases. Therefore, a detailed knowledge of these receptors is mandatory for the development of specific treatments. In this review, we summarize the current knowledge about four key C-type lectins whose importance has been steadily growing in recent years, focusing in particular on how glycan recognition takes place at the molecular level, but also looking at recent progresses in the quest for therapeutics.

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Nonhydrolyzable C-disaccharides, a new class of DC-SIGN ligands

Cited by 15 publications

References 51 publications

Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

Polyvalent C-glycomimetics based on l-fucose or d-mannose as potent DC-SIGN antagonists

Fucosylated inhibitors of recently identified bangle lectin from Photorhabdus asymbiotica

Molecular Recognition in C‐Type Lectins: The Cases of DC‐SIGN, Langerin, MGL, and L‐Sectin

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