Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

Pavão, Mauro S.G.

doi:10.1590/s0001-37652002000100007

Cited by 23 publications

(22 citation statements)

References 42 publications

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“…DS isolated from porcine intestinal mucosa and containing primarily (ϳ90%) 4-O-sulfated disaccharides was included in these experiments and used to make sulfated and desulfated fractions. Two types of DS isolated from Ascidiacea, S. plicata and A. nigra, with primarily disulfated disaccharides, 2/4-O-and 2/6-O-sulfated, respectively, were also evaluated (17,20). In addition, disaccharide analysis was also performed on DS isolated from mouse and human wound fluid, which was shown previously to be active in promoting FGF-2-and FGF-7-dependent cell proliferation (1, 7).…”

Section: -O-sulfation Of the Ds Oligosaccharides Is Required For Promentioning

confidence: 99%

Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity

Taylor

Rudisill

Gallo

2005

Journal of Biological Chemistry

102

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Glycosaminoglycans have been implicated in the binding and activation of a variety of growth factors, cytokines, and chemokines. In this way, glycosaminoglycans are thought to participate in events such as development and wound repair. In particular, heparin and heparan sulfate have been well studied, and specific aspects of their structure dictate their participation in a variety of activities. In contrast, although dermatan sulfate participates in many of the same biological processes as heparin and heparan sulfate, the interactions of dermatan sulfate have been less well studied. Dermatan sulfate is abundant in the wound environment and binds and activates growth factors such as fibroblast growth factor-2 (FGF-2) and FGF-7, which are present during the wound repair process. To determine the minimum size and sulfation content of active dermatan sulfate oligosaccharides, dermatan sulfate was first digested and then separated by size exclusion high pressure liquid chromatography, and the activity to facilitate FGF-2 and FGF-7 was assayed by the cellular proliferation of cell lines expressing FGFR1 or FGFR2 IIIb. The minimum size required for the activation of FGF-2 was an octasaccharide and for FGF-7 a decasaccharide. Active fractions were rich in monosulfated, primarily 4-O-sulfated, disaccharides and iduronic acid. Increasing the sulfation to primarily 2/4-O-sulfated and 2/6-O-sulfated disaccharides did not increase activity. Cell proliferation decreased or was abolished with higher sulfated dermatan sulfate preparations. This indicated a preference for specific dermatan sulfate oligosaccharides capable of promoting FGF-2-and FGF-7-dependent cell proliferation. These data identify critical oligosaccharides that promote specific members of the FGF family that are important for wound repair and angiogenesis.Components of the extracellular matrix are broken down following injury or inflammation. These extracellular matrix products in turn participate in various phases of the wound repair process. Following injury, proteoglycans (PG) 1 and their glycosaminoglycan (GAG) chains are released and become soluble and abundant in fluids collected from wounds (1). Dermatan sulfate (DS) is the most common GAG in the skin and is estimated to comprise between 36 and 78% of the total sulfated GAG in wound fluid samples (1). DS consists of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid (GlcA)-linked ␤134 and ␤133, respectively. Similar to modifications in heparin and heparan sulfate (HS) but distinct from the other chondroitin sulfates (CS), the GlcA of DS undergoes epimerization of the C-5 carbon, resulting in iduronic acid (IdoUA). In addition, sulfation modifications can occur at the 2-position of the uronic acid and at the 4-or 6-position of the N-acetylgalactosamine residue. GAGs and their PG core proteins participate in a variety of functions during wound healing, including binding multiple growth factors and promoting their activities (1-8). Of these activities, the fibroblast growth factor ...

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Section: -O-sulfation Of the Ds Oligosaccharides Is Required For Promentioning

confidence: 99%

Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity

Taylor

Rudisill

Gallo

2005

Journal of Biological Chemistry

102

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“…The structural requirements for the medical actions of the ascidian DSs have been proposed primarily for their anticoagulant properties since this is the most studied medical activity of this tunicate GAG type. 19,72,73 Conversely, therapeutic effects of the ascidian DSs have also been studied in other systems such as bleeding, 20 thrombosis, 20,74 cancer metastasis, 74 and inflammation. 74 The activity of the ascidians' DSs in thrombosis, cancer and inflammation seems to be driven mostly by an antiselectin mechanism.…”

Section: Ascidian Dsmentioning

confidence: 99%

“…Based on a comparative structure-function relationship study, the structural requirements observed for the anticoagulant effects of the ascidian DSs are the presence and high concentrations of the 4-sulfation in GalNAc combined with 2-sulfation in IdoA. 19,72,73 …”

Section: Ascidian Dsmentioning

confidence: 99%

NMR structural determination of unique invertebrate glycosaminoglycans endowed with medical properties

Pomin

2015

Carbohydrate Research

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“…(Holothuroidea) (Mulloy et al 2004) and sea urchins (Echinoidea) (Pomin & Mourão, 2008;Vilela-Silva et al, 2008) or ascidians (Urochordata, Ascidiacea) (Mourão & Perlin, 1987;Santos et al, 1992;Pavão et al, 1995;Pavão et al, 1998;Vicente et al, 2001;Pavão, 2002). The SF ( sea urchin eggs.…”

Section: The Trends For Regular Chemical Structures In Invertebrates mentioning

confidence: 99%

Structure versus anticoagulant and antithrombotic actions of marine sulfated polysaccharides

Pomin¹,

Mourão²

2012

Rev. bras. farmacogn.

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Marine sulfated polysaccharides (MSP), such as sulfated fucans (SF), sulfated galactans (SG) and glycosaminoglycans (GAG) isolated from either algae or invertebrate animals, are highly anionic polysaccharides capable of interacting with certain cationic proteins, such as (co)-factors of the coagulation cascade during clotting-inhibition processes. These molecular complexes between MSP and coagulation-related proteins might, at first glance, be assumed to be driven mostly by electrostatic interactions. However, a systematic comparison using several novel sulfated polysaccharides composed of repetitive oligosaccharides with clear sulfation patterns has shown that these molecular interactions are regulated essentially by the stereochemistry of the glycans (which depends on a conjunction of anomericity, monosaccharide, conformational preference, and glycosylation and sulfation sites), rather than just a simple consequence of their negative charge density (mainly the number of sulfate groups). Here, we present an overview of the structure-function relationships of MSP, correlating their structures with their potential anticoagulant and antithrombotic actions, since pathologies related to the cardiovascular system are one of the major causes of illness and mortality in the world.

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Structure and anticoagulant properties of sulfated glycosaminoglycans from primitive Chordates

Cited by 23 publications

References 42 publications

Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity

Structural and Sequence Motifs in Dermatan Sulfate for Promoting Fibroblast Growth Factor-2 (FGF-2) and FGF-7 Activity

NMR structural determination of unique invertebrate glycosaminoglycans endowed with medical properties

Structure versus anticoagulant and antithrombotic actions of marine sulfated polysaccharides

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