A Functional Dermatan Sulfate Epitope Containing Iduronate(2-O-sulfate)α1–3GalNAc(6-O-sulfate) Disaccharide in the Mouse Brain

Bao, Xingfeng; Pavão, Mauro S.G.; Santos, Joana C.; Sugahara, Kazuyuki

doi:10.1074/jbc.m503036200

Cited by 45 publications

(27 citation statements)

References 53 publications

(77 reference statements)

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supporting

confidence: 81%

“…The neurite outgrowth studies confirm the results obtained by Bao et al using libraries of natural saccharides 7 . Both groups also use blocking antibodies against selected epitopes 2,7 , and these tools should prove very useful for investigating epitope expression and function in vivo. The new study demonstrates that integration of diverse experimental platforms provides an effective approach for investigating the ways in which GAGs encode functional information in a sequence-specific manner 2 .…”

supporting

confidence: 81%

“…The authors focused on a small set of saccharides anticipated to effect neurite outgrowth based on previous studies involving natural structures 7 . The functionalized sugars were synthesized by highly convergent chemistry that allowed for incorporation of specific sulfation sequences on these carbohydrate templates as well as stereocontrol of the glycosylation reactions.…”

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confidence: 99%

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Synthetic sugars enhance the functional glycomics toolkit

Turnbull

Linhardt

2006

Nat Chem Biol

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Glycosaminoglycan-protein interactions are an important frontier for discovering new mechanisms of cellular regulation by complex sugars. The integration of the 'chemical glycomics' strategies of synthetic chemistry, arrays and biological assays shows that the precise pattern of sugar sulfation dictates the specificity of a sugar's function.Understanding the complex functions of the glycome-the repertoire of sugars expressed by cells, tissues and organisms-is a substantial challenge in the postgenome era. Glycosaminoglycans (GAGs) are an important class of complex sugars whose structurally diverse polysaccharide chains contain large amounts of information 1 that is linked to an extensive range of biological functions. However, an understanding of the mode of glycan specificity underlying these functions has proven elusive 1 . A paper by Gama et al. published in this issue of Nature Chemical Biology reports the synthesis of a set of chondroitin sulfate (CS) tetrasaccharides whose interactions and bioactivity provide evidence for a 'sulfation code' in which recognition of selected proteins is conferred by specific sequences 2 . The use of a unique combination of synthetic chemistry, microarray technology and biological assays indicates a way forward for future studies aimed at understanding the selectivity and functions of GAG structures.Questions concerning the specificity of GAG-protein interactions abound and can only be definitively addressed using fully characterized compounds. The difficulty of obtaining such structures from nature is a significant bottleneck, and the development of tools and technologies to evaluate these molecules lags behind that of genomics and proteomics. Fortunately, the field is rapidly changing 3 . For instance, chemical synthesis avoids many of the purification problems that plague natural-products chemistry. In addition, large-scale interrogation of glycan-proteins is now possible, allowing the discovery of new molecular liaisons. In particular, recent studies describe new approaches for obtaining arrayed displays of both natural 4 and synthetic 5 GAG structures from the heparan sulfate-heparin family.Initial efforts in glycosynthesis, such as those by Lopin et al., demonstrated that chondroitin saccharides can be effectively synthesized in a highly convergent and efficient manner 6 . Gama et al. 2 extend these concepts by emphasizing the value of integrative science in NIH Public Access

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supporting

confidence: 81%

supporting

confidence: 81%

mentioning

confidence: 99%

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Synthetic sugars enhance the functional glycomics toolkit

Turnbull

Linhardt

2006

Nat Chem Biol

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“…These octasaccharides are derived from the corresponding parent decasaccharide sequences flanked by two IdoUA residues in E-CS/DS (TABLE THREE) as in the case of the PTN-unbound octasaccharides (TABLE TWO). Notably, we have now verified iD units, whose existence in the mouse cerebellum was previously suggested based on the immunostaining with the iD-specific monoclonal antibody, 2A12, raised against ascidian DS (20).…”

Section: Subfractionsmentioning

confidence: 73%

“…7). Importantly, we have recently demonstrated that a unique iD (IdoUA(2-O-sulfate)-GalNAc(6-O-sulfate))-containing epitope is spatiotemporally expressed in particular regions of the developing mouse brain (20) and appears to be involved in the formation of neurites in cultured embryonic mouse * The work performed in Kobe was supported in part by HAITEKU (2004HAITEKU ( -2008) from the Japan Private School Promotion Foundation and Grants-in-Aid for Exploratory Research 17659020, Scientific Research-B 16390026, and Scientific Research on Priority Areas 14082207 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The costs of publication of this article were defrayed in part by the payment of page charges.…”

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confidence: 99%

Demonstration of the Pleiotrophin-binding Oligosaccharide Sequences Isolated from Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains of Embryonic Pig Brains

Bao

Muramatsu

Sugahara

2005

Journal of Biological Chemistry

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Mammalian brains contain significant amounts of chondroitin sulfate (CS), dermatan sulfate (DS), and CS/DS hybrid chains. CS/DS chains isolated from embryonic pig brains (E-CS/DS) promote the outgrowth of neurites in embryonic mouse hippocampal neurons in culture by interacting with pleiotrophin (PTN), a heparin-binding growth factor. Here, we analyzed oligosaccharides isolated from E-CS/DS, which showed that octasaccharides were the minimal size capable of interacting with PTN at a physiological salt concentration. Five and eight sequences were purified from fluorescently labeled PTN-bound and -unbound octasaccharide fractions, respectively, by enzymatic digestion followed by PTN-affinity chromatography. Their sequences were determined by enzymatic digestion in conjunction with high performance liquid chromatography, revealing a critical role for oversulfated D and/or iD disaccharides in the low yet significant affinity for PTN, which is required for neuritogenesis. The critical D and iD units are GlcUA(2-O-sulfate)␤1-3GalNAc(6-O-sulfate) and IdoUA(2-O-sulfate)␣1-3GalNAc(6-O-sulfate), respectively, where IdoUA represents L-iduronic acid. In contrast, high affinity interactions with PTN required decasaccharides with E units (GlcUA␤1-3GalNAc(4, 6-O-disulfate)), B units (GlcUA(2-O-sulfate)␤1-3GalNAc(4-O-sulfate)), and/or their IdoUA-containing counterparts (iE and iB) in addition to D/iD units, although the biological significance of such strong interactions remains to be investigated. Thus, chain size and composition are crucial to the interaction with PTN, and PTN binds to multiple sequences in E-CS/DS chains with distinct affinity. Notably, not only heparan sulfate but also CS/DS hybrid chain structures of mammalian brains contain a high degree of microheterogeneity with a cluster of oversulfated disaccharides and appear to play roles in regulating the functions of PTN.Chondroitin sulfate (CS) 4 and dermatan sulfate (DS), a class of glycosaminoglycan (GAG)-type polysaccharides, occur covalently attached to proteoglycan (PG) core proteins (1). Like heparan sulfate (HS), another class of GAGs, CS/DS chains are abundant at cell surfaces and in the extracellular matrices. They regulate cell division, adhesion, and morphogenesis through direct binding to secreted signaling proteins, thereby modulating their activities, or through interactions with extracellular matrix molecules (2-6, for reviews, see a Ref. 7). CS and DS typically have backbones consisting of repeating disaccharide units of -GlcUA-GalNAc-and -IdoUA-GalNAc-, respectively, where IdoUA represents L-iduronic acid. Notably, hybrid chains, composed of both units in varying proportions, also exist (8). These units are modified during chain elongation by specific sulfotransferases at C-2 of GlcUA/ IdoUA and/or C-4 and/or C-6 of GalNAc in various combinations, thereby producing characteristic sulfation patterns and enormous structural diversity. These structural characteristics are strictly regulated, as revealed by the compositional analysis of CS/DS chai...

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Proteoglycans and Acidic Polysaccharides Analysis

Lauder

2015

Encyclopedia of Analytical Chemistry

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The study of the structure and function of proteoglycans (PGs) and glycosaminoglycans (GAGs) has assumed an increasing significance as the wide range of important biological processes in which they play central roles has been elucidated. As studies of GAG structure expand in scope, and detail, the full structural diversity of these polymers is being uncovered. Significant heterogeneity can be seen but relationships with development, age, and pathology are being uncovered, which place these macromolecules centrally in these processes. Available methodologies allow detailed analysis of GAGs, but careful attention to the sample requirements of these methods and to their limitations is required to ensure the quality and reliability of the data derived is assured. Important developments, including mass spectrometry approaches, will take the field forward but well‐established methods for the isolation and characterization of these complex molecules continue to have a hugely important role to play in structural and functional studies. This article examines a wide range of methodologies for the isolation and characterization of the PGs and GAGs in which recent developments in the field are reported along with well‐established methods for the characterization of entire GAG chains or discrete features within those.

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A Functional Dermatan Sulfate Epitope Containing Iduronate(2-O-sulfate)α1–3GalNAc(6-O-sulfate) Disaccharide in the Mouse Brain

Cited by 45 publications

References 53 publications

Synthetic sugars enhance the functional glycomics toolkit

Synthetic sugars enhance the functional glycomics toolkit

Demonstration of the Pleiotrophin-binding Oligosaccharide Sequences Isolated from Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains of Embryonic Pig Brains

Proteoglycans and Acidic Polysaccharides Analysis

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