Conformational behaviour of glycomimetics: NMR and molecular modelling studies of the C-glycoside analogue of the disaccharide methyl β-d-galactopyranosyl-(1→3)-β-d-glucopyranoside

Vidal, Paloma; Vauzeilles, Boris; Blériot, Yves; Sollogoub, Matthieu; Sînaÿ, Pierre; Jiménez‐Barbero, Jesús; Espinosa, Juan F.

doi:10.1016/j.carres.2007.04.017

Cited by 18 publications

(42 citation statements)

References 23 publications

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“…4). The ensemble of major conformations observed correspond to a low-energy population in solution (35). In addition, the size of the binding site was maintained almost constant during the entire simulation (Fig.…”

Section: With Lacto-n-biosementioning

confidence: 93%

NMR and MD Investigations of Human Galectin-1/Oligosaccharide Complexes

Meynier

Feracci

Espéli

et al. 2009

Biophysical Journal

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The specific recognition of carbohydrates by lectins plays a major role in many cellular processes. Galectin-1 belongs to a family of 15 structurally related beta-galactoside binding proteins that are able to control a variety of cellular events, including cell cycle regulation, adhesion, proliferation, and apoptosis. The three-dimensional structure of galectin-1 has been solved by x-ray crystallography in the free form and in complex with various carbohydrate ligands. In this work, we used a combination of two-dimensional NMR titration experiments and molecular-dynamics simulations with explicit solvent to study the mode of interaction between human galectin-1 and five galactose-containing ligands. Isothermal titration calorimetry measurements were performed to determine their affinities for galectin-1. The contribution of the different hexopyranose units in the protein-carbohydrate interaction was given particular consideration. Although the galactose moiety of each oligosaccharide is necessary for binding, it is not sufficient by itself. The nature of both the reducing sugar in the disaccharide and the interglycosidic linkage play essential roles in the binding to human galectin-1.

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Section: With Lacto-n-biosementioning

confidence: 93%

NMR and MD Investigations of Human Galectin-1/Oligosaccharide Complexes

Meynier

Feracci

Espéli

et al. 2009

Biophysical Journal

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“…4), and its associated stereoelectronic effects radically differentiate the conformational properties of glycosides from those of structures based on cyclohexane or those in which the linking oxygen is replaced by a methylene group (C-glycosides) [78]. Ultimately, the degree to which a force field is able to correctly reproduce the stability and conformation of the carbohydrate ring and the interactions between the rings depend on a delicate balance between inter- and intramolecular forces [28].…”

Section: Carbohydrate Force Fieldsmentioning

confidence: 99%

“…4) in hexopyranoses. In fact, the weakening of 1–4 interactions (O6–O5), relative to 1–5 (O6–O4), prevents the accurate fitting of the rotational properties for this linkage [78,90]. Conversely, choosing not to use 1–4 scaling factors may cause a conflict with the treatment of non-bonded interactions in protein force fields.…”

Section: Carbohydrate Force Fieldsmentioning

confidence: 99%

Molecular simulations of carbohydrates and protein–carbohydrate interactions: motivation, issues and prospects

Fadda

Woods

2010

Drug Discovery Today

174

122

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The characterization of the 3D structure of oligosaccharides, their conjugates and analogs is particularly challenging for traditional experimental methods. Molecular simulation methods provide a basis for interpreting sparse experimental data and for independently predicting conformational and dynamic properties of glycans. Here, we summarize and analyze the issues associated with modeling carbohydrates, with a detailed discussion of four of the most recently developed carbohydrate force fields, reviewed in terms of applicability to natural glycans, carbohydrate–protein complexes and the emerging area of glycomimetic drugs. In addition, we discuss prospectives and new applications of carbohydrate modeling in drug discovery.

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“…As foundation for this study, the conformational behavior of compounds 1 and 2 ( Figure 1) in water solution deduced previously by combination of NMR experiments and molecular mechanics calculations was used. [9] The employed protocol involved the calculation of the potential energy maps for both compounds by using the Maestro package, [10] followed by the determination of the expected vicinal protonproton couplings (J) and nuclear Overhauser effects (NOEs) for the calculated population distribution. The theoretical data for the ensemble average was compared to the obtained experimental NMR data to validate the theoretical results and to estimate the actual population distribution in solution.…”

Section: Resultsmentioning

confidence: 99%

Conformational Selection in Glycomimetics: Human Galectin‐1 Only Recognizes syn‐Ψ‐Type Conformations of β‐1,3‐Linked Lactose and Its C‐Glycosyl Derivative

Vidal

Roldós

Fernández‐Alonso

et al. 2013

Chemistry A European J

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The human lectin galectin-1 (hGal-1) translates sugar signals, that is, β-galactosides, into effects on the level of cells, for example, growth regulation, and has become a model for studying binding of biopharmaceutically relevant derivatives. Bound-state conformations of Galβ-C-(1→3)-Glcβ-OMe (1) and its βGal-(1→3)-βGlc-OMe disaccharide parent compound were studied by using NMR spectroscopy (transferred (TR)-NOESY data), assisted by docking experiments and molecular dynamics (MD) simulations. The molecular recognition process involves a conformational selection event. Although free C-glycoside access four distinct conformers in solution, hGal-1 recognizes shape of a local minimum of compound 1, the syn-Φ/syn-Ψ conformer, not the structure at global minimum. MD simulations were run to explain, in structural terms, the observed geometry of the complex.

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Conformational behaviour of glycomimetics: NMR and molecular modelling studies of the C-glycoside analogue of the disaccharide methyl β-d-galactopyranosyl-(1→3)-β-d-glucopyranoside

Cited by 18 publications

References 23 publications

NMR and MD Investigations of Human Galectin-1/Oligosaccharide Complexes

NMR and MD Investigations of Human Galectin-1/Oligosaccharide Complexes

Molecular simulations of carbohydrates and protein–carbohydrate interactions: motivation, issues and prospects

Conformational Selection in Glycomimetics: Human Galectin‐1 Only Recognizes syn‐Ψ‐Type Conformations of β‐1,3‐Linked Lactose and Its C‐Glycosyl Derivative

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