Synthesis of Lactose Dendrimers and Multivalency Effects in Binding to the Cholera Toxin B Subunit

Vrasidas, Ioannis; Mol, Nico J. de; Liskamp, Rob M. J.; Pieters, Roland J.

doi:10.1002/1099-0690(200112)2001:24<4685::aid-ejoc4685>3.0.co;2-9

Cited by 82 publications

(63 citation statements)

References 13 publications

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“…Murine EHS laminin [19b] and recombinant human Mac-2 BP produced in human embryonic kidney cells [21e] were kindly provided by R. Timpl (Munich, Germany). The glycodendrimers were synthesized as described, [41] coupling protected lactose isothiocyanate 1 (see Figure 1) to our dendrimer scaffolds based on 3,5-di-(2-aminoethoxy)benzoic acid repeating units carrying 2, 4, and 8 amino groups, respectively. The acetate-protected lactose isothiocyanate 1 was prepared starting from lactose following an established method.…”

Section: Discussionmentioning

confidence: 99%

Wedgelike Glycodendrimers as Inhibitors of Binding of Mammalian Galectins to Glycoproteins, Lactose Maxiclusters, and Cell Surface Glycoconjugates

et al. 2001

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Galectins are mammalian carbohydrate-binding proteins that are involved in cell-cell and cell-matrix adhesion, cell migration, and growth regulation with relevance to inflammation and tumor spread. These important functions account for the interest to design suitable low molecular weight inhibitors that match the distinct modes of presentation of the carbohydrate recognition domains of the different galectin subfamilies. Using 3,5-di-(2-aminoethoxy)benzoic acid as the branching unit, wedgelike glycodendrimers with two, four, and eight lactose moieties (G1-G3) were synthesized. They were tested in solid-phase competition assays with lactose maxiclusters and various N-glycan branching profiles (miniclusters) as the matrix and also in cell assays. Prototype galectins-1 and -7, chimera-type galectin-3, a plant (AB)(2) toxin, and a lactose-binding immunoglobulin G fraction from human serum were the carbohydrate-binding targets. Potent inhibition and remarkable cluster effects were seen for the homodimeric galectin-1, especially in combination with biantennary N-glycans as the matrix. Remarkably, for the tetravalent G2 glycodendrimer, the inhibitory potency of each lactose unit reached a maximum value of 1667 relative to free lactose. In haemagglutination experiments as a model for cell adhesion, galectin-3 was markedly sensitive to increased sugar valency and a relative potency per lactose of 150 was reached. The spatial orientation of the carbohydrate recognition domains of the endogenous lectins and the branching pattern of the carbohydrates of the glycoprotein matrices used are both important factors in the design and synthesis of glycodendrimers with galectin-selective properties.

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Section: Discussionmentioning

confidence: 99%

Wedgelike Glycodendrimers as Inhibitors of Binding of Mammalian Galectins to Glycoproteins, Lactose Maxiclusters, and Cell Surface Glycoconjugates

et al. 2001

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“…The neoganglioprotein containing an average of two to three ganglioside GM 1 -derived oligosaccharide chains was prepared by covalently linking the sphingosine N-alkyl(sulfosuccinimidyl)ester derivative of lysoganglioside GM 1 , which had been activated by treatment with bis(sulfosuccinimidyl)suberate to carbohydrate-free bovine serum albumin as described . Wedge-like glycodendrimers with 3,5-di(2-aminoethoxy)benzoic acid as a branching unit and two or four lactose head groups as galectin-reactive ligand were prepared and analysed for purity by NMR spectroscopy and mass spectrometry as described Vrasidas et al, 2001). Cholera toxin B subunit was purchased from Sigma (Munich, Germany).…”

Section: Reagentsmentioning

confidence: 99%

Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells

et al. 2003

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The extracellular functions of galectin-7 (p53-induced gene 1) are largely unknown. On the surface of neuroblastoma cells (SK-N-MC), the increased GM 1 density, a result of upregulated ganglioside sialidase activity, is a key factor for the switch from proliferation to differentiation. We show by solid-phase and cell assays that the sugar chain of this ganglioside is a ligand for galectin-7. In serum-supplemented proliferation assays, galectin-7 reduced neuroblastoma cell growth without the appearance of features characteristic for classical apoptosis. The presence of galectin-3 blocked this effect, which mechanistically resembles that of galectin-1. By virtue of carbohydrate binding, galectin-7 thus exerts neuroblastoma growth control similar to galectin-1 despite their structural differences. In addition to p53-linked proapoptotic activity intracellularly, galectin-7, acting as a lectin on the cell surface, appears to be capable of reducing cancer cell proliferation in susceptible systems.

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“…Initially the group conjugated first-, second-, and third-generation dendrimers with 2, 4, or 8 lactose groups, respectively, using thiourea linkages (Figure 3). 45 Using a direct fluorescence binding assay, the group observed apparent dissociation constants (K d values) of 235, 99, and 33 μM for the divalent, tetravalent, and octavalent glycodendrimers, respectively. The modest multivalency effect in this study was related to the better ability of the higher generation glycodendrimers to bridge the binding sites between toxin molecules compared to the first-generation analogue.…”

Section: Types Of Antimicrobial Dendrimersmentioning

confidence: 99%

Exploiting Dendrimer Multivalency To Combat Emerging and Re-Emerging Infectious Diseases

et al. 2011

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The emergence and re-emergence of bacterial strains that are resistant to current antibiotics reveals the clinical need for new agents that possess broad-spectrum antibacterial activity. Furthermore, bacteriophobic coatings that repel bacteria are important for medical devices, as the lifetime, reliability, and performance of implant devices are hindered by bacterial adhesion and infection. Dendrimers, a specific class of monodisperse macromolecules, have recently shown potential to function as both antibacterial agents as well as antimicrobial surface coatings. This review discusses the limitations with currently used antibacterial agents and describes how various classes of dendrimers, including glycodendrimers, cationic dendrimers, anionic dendrimers, and peptide dendrimers, have the potential to improve upon or replace certain antibiotics. Furthermore, the unexplored areas in this field of research will be mentioned to present opportunities for additional studies regarding the use of dendrimers as antimicrobial agents.

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Synthesis of Lactose Dendrimers and Multivalency Effects in Binding to the Cholera Toxin B Subunit

Cited by 82 publications

References 13 publications

Wedgelike Glycodendrimers as Inhibitors of Binding of Mammalian Galectins to Glycoproteins, Lactose Maxiclusters, and Cell Surface Glycoconjugates

Wedgelike Glycodendrimers as Inhibitors of Binding of Mammalian Galectins to Glycoproteins, Lactose Maxiclusters, and Cell Surface Glycoconjugates

Homodimeric galectin-7 (p53-induced gene 1) is a negative growth regulator for human neuroblastoma cells

Exploiting Dendrimer Multivalency To Combat Emerging and Re-Emerging Infectious Diseases

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