Synthesis of multivalent <i>S</i>-glycoside analogs of a heparan sulfate sequence

Teki, Dindet Steve-Evanes Koffi; Bil, Abed; Moreau, Vincent; Chagnault, Vincent; Bamba, Fanté; Adjou, Ané; Kovensky, José

doi:10.1039/c9qo00581a

Cited by 14 publications

(14 citation statements)

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“…The most common modifications, developed to resist hydrolysis by glycosidases, are S- glycosides and C- glycosides. The long in vivo lifetime − made these analogues useful for therapeutic applications, , as shown in the case of the S- linked antitumor agent Landomycin A (Figure ). In addition to in vivo stability, a collection of short β-1,3-glycan thioglycoside derivatives showed an enhanced affinity for hydrophobic binding pockets of various lectins, dectins, and receptors such as the complement receptor 3 (CR3). − Following a similar idea, the synthesis of S- linked oligosialic acid antigens was reported for the development of carbohydrate-based vaccines (Figure ).…”

Section: Chemically Modified Oligosaccharidesmentioning

confidence: 99%

Structural Studies Using Unnatural Oligosaccharides: Toward Sugar Foldamers

et al. 2019

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Biopolymers, like DNA and proteins, fold in specific conformations in order to exert complex biological functions. Synthetic modifications are commonly used to alter those conformations and create engineered biomaterials. In stark contrast, the chemical complexity and dynamic nature of polysaccharides have hampered a detailed structural characterization and structure−function correlations are still incomplete. Many synthetic strategies have been developed to access complex unnatural oligosaccharides, capable of mimicking or even improving the properties of the natural counterpart. However, the structural features behind these results are often neglected. This perspective highlights the approaches adopted to develop unnatural glycans, with a particular focus on how the insertion of specific modifications results in more flexible or more constrained structures. Synthetic analogues of natural oligosaccharides could shine light on fundamental structural features. The combination of modern synthetic, computational, and analytical methods will result in novel carbohydrate based foldamers, with defined shape and aggregation behavior. Multiple applications in biology, material science, and nanotechnology can be envisioned.

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Section: Chemically Modified Oligosaccharidesmentioning

confidence: 99%

Structural Studies Using Unnatural Oligosaccharides: Toward Sugar Foldamers

et al. 2019

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“…In our previous work, 20 the S -disaccharide 4 was prepared using precursors 1 and 2 (Scheme 1). Compound 1 was obtained in four steps from d -glucurono-6,3-lactone in an overall yield of 38%, whereas compound 2 required five steps starting from methyl α- d -galactopyranoside and was obtained in 52% yield.…”

Section: Resultsmentioning

confidence: 99%

“…For the preparation of compound 1 , treatment of d -glucurono-3,6-lactone with sodium hydroxide in methanol followed by acetylation afforded the per acetylated methyl glucuronate 7 in 80% yield, which was converted to the bromide 8 in 88% yield. 20 Two different routes were then explored for the preparation of the 1-thiol glucuronic acid 1 .…”

Section: Resultsmentioning

confidence: 99%

“…NMR spectra of the product showed the presence of two compounds; in fact the thiodisaccharide was obtained as an α/β mixture, as anomerisation of the thiol 1 occurs in the reaction medium. 20 After several unsuccessful separation attempts by silica gel chromatography, we finally isolated the desired β anomer by crystallisation in methanol (67% yield). The stereochemistry of 11 was confirmed by NMR: H-1′ appears at 5.06 ppm with a trans -diaxial J of 10.1 Hz.…”

Section: Resultsmentioning

confidence: 99%

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Synthesis of novel S- and O-disaccharide analogs of heparan sulfate for heparanase inhibition

et al. 2022

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“… 14 , 15 Within this context, unnatural sequences such as those obtained from the replacement of glycosidic linkage oxygen with sulfur ( S -glycosides, Figure 1 b) offer the exciting possibility of studying unique conformational preferences about the thioglycosidic and aglyconic bonds. 16 − 18 Subsequent comparison to native sequences will improve our understanding and capability to perturb HS structure-to-function relationships as well as access the untapped carbohydrate chemical space.…”

Section: Introductionmentioning

confidence: 99%

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate

et al. 2022

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Heparan sulfate (HS), a sulfated linear carbohydrate that decorates the cell surface and extracellular matrix, is ubiquitously distributed throughout the animal kingdom and represents a key regulator of biological processes and a largely untapped reservoir of potential therapeutic targets. The temporal and spatial variations in the HS structure underpin the concept of “heparanome” and a complex network of HS binding proteins. However, despite its widespread biological roles, the determination of direct structure-to-function correlations is impaired by HS chemical heterogeneity. Attempts to correlate substitution patterns (mostly at the level of sulfation) with a given biological activity have been made. Nonetheless, these do not generally consider higher-level conformational effects at the carbohydrate level. Here, the use of NMR chemical shift analysis, NOEs, and spin–spin coupling constants sheds new light on how different sulfation patterns affect the polysaccharide backbone geometry. Furthermore, the substitution of native O -glycosidic linkages to hydrolytically more stable S -glycosidic forms leads to observable conformational changes in model saccharides, suggesting that alternative chemical spaces can be accessed and explored using such mimetics. Employing a series of systematically modified heparin oligosaccharides (as a proxy for HS) and chemically synthesized O - and S -glycoside analogues, the chemical space occupied by such compounds is explored and described.

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Synthesis of multivalent S-glycoside analogs of a heparan sulfate sequence

Abstract: In this article, we report on the synthesis of new glycoclusters with thiodisaccharide units, S-analogs of heparan sulfate.

Cited by 14 publications

References 24 publications

Structural Studies Using Unnatural Oligosaccharides: Toward Sugar Foldamers

Structural Studies Using Unnatural Oligosaccharides: Toward Sugar Foldamers

Synthesis of novel S- and O-disaccharide analogs of heparan sulfate for heparanase inhibition

Using NMR to Dissect the Chemical Space and O-Sulfation Effects within the O- and S-Glycoside Analogues of Heparan Sulfate

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