Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications

Baráth, Marek; Hansen, Steen U.; Dalton, Charlotte; Jayson, Gordon C; Miller, Gavin J.; Gardiner, John M.

doi:10.3390/molecules20046167

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…Furthermore, the polymerization of the various disaccharides necessitates stereo-specific formation of a-glycosidic and b-glycosidic linkages. Considerable progress, however, has been made, both for HS [110][111][112][113][114][115] and for CS [116][117][118][119][120]. An emerging and powerful approach is the use of chemoenzymatic strategies [120], which are based on knowledge of HS biosynthesis [104] and HS biosynthetic enzymes [122][123][124].…”

Section: The Structures Recognized By Chemokinesmentioning

confidence: 99%

The sweet spot: how GAGs help chemokines guide migrating cells

Monneau

Arenzana-Seisdedos

Lortat‐Jacob

2015

Journal of Leukocyte Biology

111

113

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Glycosaminoglycans are polysaccharides that occur both at the cell surface and within extracellular matrices. Through their ability to bind to a large array of proteins, almost 500 of which have been identified to date, including most chemokines, these molecules regulate key biologic processes at the cell-tissue interface. To do so, glycosaminoglycans can provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and can also directly contribute to biologic activities or signaling processes. The binding of chemokines to glycosaminoglycans, which, at the biochemical level, has been mostly studied using heparin, has traditionally been thought of as a mechanism for maintaining haptotactic gradients within tissues along which cells can migrate directionally. Many aspects of chemokine-glycosaminoglycan interactions, however, also suggest that the formation of these complexes could serve additional purposes that go well beyond a simple immobilization process. In addition, progress in glycobiology has revealed that glycosaminoglycan structures, in term of length, sulfation, and epimerization pattern, are specific for cell, tissue, and developmental stage. Glycosaminoglycan regulation and glycosaminoglycan diversity, which cannot be replicated using heparin, thus suggests that these molecules may fine-tune the immune response by selectively recruiting specific chemokines to cell surfaces. In this context, the aim of the present text is to review the chemokine-glycosaminoglycan complexes described to date and provide a critical analysis of the tools, molecules, and strategies that can be used to structurally and functionally investigate the formation of these complexes.

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Section: The Structures Recognized By Chemokinesmentioning

confidence: 99%

The sweet spot: how GAGs help chemokines guide migrating cells

Monneau

Arenzana-Seisdedos

Lortat‐Jacob

2015

Journal of Leukocyte Biology

111

113

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“…Gardiner and co‐workers’ also reported a synthetic approach to a small matrix of protected heparin‐type oligosaccharides containing orthogonal d ‐GlcN O ‐6 protecting groups [26] . Building on their earlier work, [27–30] this was completed to demonstrate capability in accessing programmability at specific sites, relevant to sulfation or other modifications.…”

Section: Synthetic Methodology Developments For Heparan Sulfate Synthesismentioning

confidence: 99%

“…Gardiner and co-workers' also reported a synthetic approach to a small matrix of protected heparin-type oligosaccharides containing orthogonal d-GlcN O-6 protecting groups. [26] Building on their earlier work, [27][28][29][30] this was completed to demonstrate capability in accessing programmability at specific sites, relevant to sulfation or other In 2018, Boons and co-workers' reported an enzymatic modification of three chemically synthesised hexasaccharides, harnessing a d-GlcN-6-OMe blocking group, to effect regiodefined enzymatic modification and provide a library of 21 hexasaccharides. [31]…”

Section: Programming For Regiodefined Hs O/n Sulfationmentioning

confidence: 99%

Developments in the Chemical Synthesis of Heparin and Heparan Sulfate

Pongener

O'Shea

Wootton

et al. 2021

The Chemical Record

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Heparin and heparan sulfate represent key members of the glycosaminoglycan family of carbohydrates and underpin considerable repertoires of biological importance. As such, their efficiency of synthesis represents a key requirement, to further understand and exploit the H/HS structure‐to‐biological function axis. In this review we focus on chemical approaches to and methodology improvements for the synthesis of these essential sugars (from 2015 onwards). We first consider advances in accessing the heparin‐derived pentasaccharide anticoagulant fondaparinux. This is followed by heparan sulfate targets, including key building block synthesis, oligosaccharide construction and chemical sulfation techniques. We end with a consideration of technological improvements to traditional, solution‐phase synthesis approaches that are increasingly being utilised.

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“… Lactone methanolysis and O -2 benzoylation gave disaccharide β-4 . We have previously accessed β-4 (and the corresponding alpha anomer) via a synthetic approach using trichloroacetimidate donors, and have employed these as glycosyl donors in the synthesis of longer H/HS-like oligosaccharides …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Heparan Sulfate- and Dermatan Sulfate-Related Oligosaccharides via Iterative Chemoselective Glycosylation Exploiting Conformationally Disarmed [2.2.2] l-Iduronic Lactone Thioglycosides

2019

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Heparan sulfate (HS) and dermatan sulfate (DS) are l-iduronic acid containing glycosaminoglycans (GAGs) which are implicated in a number of biological processes and conditions including cancer and viral infection. Chemical synthesis of HS and DS is required to generate structurally defined oligosaccharides for a biological study. Herein, we present a new synthetic approach to HS and DS oligosaccharides using chemoselective glycosylation which relies on a disarmed [2.2.2] l-ido lactone motif. The strategy provides a general approach for iterative-reducing end chain extension, using only shelf-stable thioglycoside building blocks, exploiting a conformational switch to control reactivity, and thus requires no anomeric manipulation steps between glycosylations.

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Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications

Cited by 14 publications

References 38 publications

The sweet spot: how GAGs help chemokines guide migrating cells

The sweet spot: how GAGs help chemokines guide migrating cells

Developments in the Chemical Synthesis of Heparin and Heparan Sulfate

Synthesis of Heparan Sulfate- and Dermatan Sulfate-Related Oligosaccharides via Iterative Chemoselective Glycosylation Exploiting Conformationally Disarmed [2.2.2] l-Iduronic Lactone Thioglycosides

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