New aspects of glycoside bond formation

Schmidt, Richard R.; Castro‐Palomino, Julio C.; Retz, Oliver

doi:10.1351/pac199971050729

Cited by 71 publications

(44 citation statements)

References 40 publications

(58 reference statements)

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“…2,3,4,6-Tetra- O -benzoyl-β-D-galactopyranosyl trichloroacetimidate ( 2 ) was synthesized according to Schmidt et al [14]. 3,4-Bis(hydroxymethyl)furan ( 1 ) was synthesized according to [50].…”

Section: Methodsmentioning

confidence: 99%

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

Marano

Gronewold²,

Frank³

et al. 2012

Beilstein J. Org. Chem.

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SummaryOligosaccharides aberrantly expressed on tumor cells influence processes such as cell adhesion and modulation of the cell’s microenvironment resulting in an increased malignancy. Schmidt’s imidate strategy offers an effective method to synthesize libraries of various oligosaccharide mimetics. With the aim to perturb interactions of tumor cells with extracellular matrix proteins and host cells, molecules with 3,4-bis(hydroxymethyl)furan as core structure were synthesized and screened in biological assays for their abilities to interfere in cell adhesion and other steps of the metastatic cascade, such as tumor-induced angiogenesis.The most active compound, (4-{[(β-D-galactopyranosyl)oxy]methyl}furan-3-yl)methyl hydrogen sulfate (GSF), inhibited the activation of matrix-metalloproteinase-2 (MMP-2) as well as migration of the human melanoma cells of the lines WM-115 and WM-266-4 in a two-dimensional migration assay. GSF inhibited completely the adhesion of WM-115 cells to the extracellular matrix (ECM) proteins, fibrinogen and fibronectin.In an in vitro angiogenesis assay with human endothelial cells, GSF very effectively inhibited endothelial tubule formation and sprouting of blood vessels, as well as the adhesion of endothelial cells to ECM proteins. GSF was not cytotoxic at biologically active concentrations; neither were 3,4-bis{[(β-D-galactopyranosyl)oxy]methyl}furan (BGF) nor methyl β-D-galactopyranoside nor 3,4-bis(hydroxymethyl)furan, which were used as controls, eliciting comparable biological activity. In silico modeling experiments, in which binding of GSF to the extracellular domain of the integrin αvβ3 was determined, revealed specific docking of GSF to the same binding site as the natural peptidic ligands of this integrin. The sulfate in the molecule coordinated with one manganese ion in the binding site.These studies show that this chemically easily accessible molecule GSF, synthesized in three steps from 3,4-bis(hydroxymethyl)furan and benzoylated galactose imidate, is nontoxic and antagonizes cell physiological processes in vitro that are important for the dissemination and growth of tumor cells in vivo.

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Section: Methodsmentioning

confidence: 99%

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

Marano

Gronewold²,

Frank³

et al. 2012

Beilstein J. Org. Chem.

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“…Of course, the linchpin of every glycosylation is the anomeric leaving group, which is needed and should be easily activated to induce the formation of the glycosidic linkage [3,6]. Numerous anomeric leaving groups have been examined and several of them are widely utitized in the synthesis of complex carbohydrates.…”

Section: Building Blocksmentioning

confidence: 99%

Classical Tools for Oligosaccharide Synthesis

Werz¹

2015

Carbohydrate Chemistry: State of the Art and Challenges for Drug Development

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The chemical synthesis of complex carbohydrates has been a challenging and difficult task for more than a century [1]. The big difference with the other two major classes of biopolymers, oligonucleotides and proteins, is that several points for further attachment (hydroxyls and amines) are commonly available at one monosaccharidic building block. Thus, even with two subunits, a variety of different dimers can be obtained. With more than two subunits, branched structures might arise as well. The situation becomes even more difficult, since a glycosidic linkage between two subunits creates a new stereogenic center. A recent statistical analysis regarding the diversity of mammalian carbohydrate structures, based on the "10 mammalian monosaccharides" without considering any further attachments, reveals astonishing numbers that dwarf the complexity of both peptides and oligonucleotides by orders of magnitude [2]. Although the number of structural combinations encountered in nature is much smaller than the theoretical ones, it is evident that glycochemists have to face a variety of challenges during the preparation of an oligosaccharide by chemical means. Carbohydrate Chemistry: State of the Art and Challenges for Drug Development Downloaded from www.worldscientific.com by UNIVERSITY OF PITTSBURGH on 10/02/15. For personal use only.

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“…Many glycosyl donors introduced during that period gave rise to excellent complimentary glycosylation methodologies. Arguably, trichloroacetimidates [29,30], thioglycosides [31][32][33] and fluorides [34,35] have become the most common glycosyl donors nowadays.…”

Section: Major Types Of O-glycosidic Linkagesmentioning

confidence: 99%

General Aspects of the Glycosidic Bond Formation

Demchenko

2008

Handbook of Chemical Glycosylation

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New aspects of glycoside bond formation

Cited by 71 publications

References 40 publications

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

An easily accessible sulfated saccharide mimetic inhibits in vitro human tumor cell adhesion and angiogenesis of vascular endothelial cells

Classical Tools for Oligosaccharide Synthesis

General Aspects of the Glycosidic Bond Formation

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