Advancing Solutions to the Carbohydrate Sequencing Challenge

Gray, Christopher; Migas, Lukasz; Barran, Perdita E.; Pagel, Kevin; Seeberger, Peter H.; Eyers, Patrick A.; Boons, Geert‐Jan; Pohl, Nicola L. B.; Compagnon, Isabelle; Widmalm, Göran; Flitsch, Sabine L.

doi:10.1021/jacs.9b06406

Cited by 121 publications

(135 citation statements)

References 150 publications

(306 reference statements)

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“…Ion mobility mass spectrometry (IMMS) of glycans has demonstrated the ability to characterise isomeric arrangements of glycan building blocks (mannose, galactose, etc. ), but also connectivity (glycosidic bond linkage, sialic acids) and configuration (α and β anomers) [15][16][17][18] . GAGs possess a linear sequence with no branching, and connectivity is singular to the GAG family.…”

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confidence: 99%

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

et al. 2020

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Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a "Shotgun" Ion Mobility Mass Spectrometry Sequencing (SIMMS 2) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di-to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3O-sulfate groups. SIMMS 2 analysis of two fibroblast growth factorinhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS 2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.

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confidence: 99%

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

et al. 2020

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“…Considering the multifold modes of monosaccharide-based polysaccharide and particularly glycan linkages, variations in saccharide compositions and sequences, linkage regio-and stereo-chemistry as well as branching diversity produces an enormous structural diversity. As a consequence of this complexity, the comprehensive assignment of covalent structures of naturally occurring polysaccharides is a major challenge to the organic chemist [104][105][106][107][108]. Indeed, no method available for structural analysis will offer sufficient data to allow the structure of a polysaccharide to be defined in the above-mentioned terms.…”

Section: Techniques For Structural Characterization Of Polysaccharidesmentioning

confidence: 99%

Exploiting the Amazing Diversity of Natural Source-Derived Polysaccharides: Modern Procedures of Isolation, Engineering, and Optimization of Antiviral Activities

et al. 2020

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Naturally occurring polysaccharide sulfates are highly diverse, owning variations in the backbone structure, linkage pattern and stereochemistry, branching diversity, sulfate content and positions of sulfate group(s). These structural characteristics bring about diverse sulfated polymers with dissimilar negative charge densities and structure–activity relationships. Herein, we start with a short discussion of techniques needed for extraction, purification, chemical sulfation, and structural characterization of polysaccharides. Processes of isolation and sulfation of plant-derived polysaccharides are challenging and usually involve two steps. In this context, we describe an integrated extraction-sulfation procedure that produces polysaccharide sulfates from natural products in one step, thereby generating additional pharmacological activities. Finally, we provide examples of the spectrum of natural source-derived polysaccharides possessing specific features of bioactivity, in particular focusing on current aspects of antiviral drug development and drug–target interaction. Thus, the review presents a detailed view on chemically engineered polysaccharides, especially sulfated derivatives, and underlines their promising biomedical perspectives.

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“…3 To decipher the complex biological and physicochemical properties of this family of biomolecules, analytical strategies are still developed. 4 Very recently, low-temperature scanning tunneling microscopy allowed direct imaging different conformers of some oligosaccharides with a sub-nanometer resolution. 5 On another side, neutron crystallography is able to study H-bond networks in protein binding sites.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of an Exhaustive Library of Naturally Occurring Galf-Manp and Galp-Manp Disaccharides. Towards Fingerprinting According to the Ring Size by Advanced Mass Spectrometry-Based IM-MS and IRMPD.

Favreau¹,

Yeni²,

Ollivier³

et al. 2021

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Nature offers a huge diversity of glycosidic derivatives. Amongst numerous structural modulations, the nature of the ring size of hexosides may induce significant differences on both biological and physicochemical properties of the glycoconjugate of interest. On this assumption, we expect that small disaccharides bearing either a furanosyl entity or a pyranosyl residue would give a specific signature, even in the gas phase. On the basis of the scope of mass spectrometry, two analytical techniques to register those signatures were considered, i.e. the ion-mobility (IM) and the infra-red multiple photon dissociation (IRMPD), in order to build up cross-linked databases. D-Galactose occurs in natural products in both tautomeric forms and presents all possible regioisomers when linked to D-mannose. Consequently, the four reducing Galf-Manp disaccharides as well as the four Galp-Manp counterparts were firstly synthesized according to a highly convergent approach, and IM-MS and IRMPD-MS data were secondly collected. Both techniques used afforded signatures, specific to the nature of the connectivity between the two glycosyl entities.

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Advancing Solutions to the Carbohydrate Sequencing Challenge

Cited by 121 publications

References 150 publications

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

Shotgun ion mobility mass spectrometry sequencing of heparan sulfate saccharides

Exploiting the Amazing Diversity of Natural Source-Derived Polysaccharides: Modern Procedures of Isolation, Engineering, and Optimization of Antiviral Activities

Synthesis of an Exhaustive Library of Naturally Occurring Galf-Manp and Galp-Manp Disaccharides. Towards Fingerprinting According to the Ring Size by Advanced Mass Spectrometry-Based IM-MS and IRMPD.

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