Holothurian Fucosylated Chondroitin Sulfate

Abstract

Fucosylated chondroitin sulfate (FucCS) is a structurally distinct glycosaminoglycan found in sea cucumber species. It has the same backbone composition of alternating 4-linked glucuronic acid and 3-linked N-acetyl galactosamine residues within disaccharide repeating units as regularly found in mammalian chondroitin sulfates. However, FucCS has also sulfated fucosyl branching units 3-O-linked to the acid residues. The sulfation patterns of these branches vary accordingly with holothurian species and account for different biological actions and responses. FucCSs may exhibit anticoagulant, antithrombotic, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities, besides its beneficial effects in hemodialysis, cellular growth modulation, fibrosis and hyperglycemia. Through an historical overview, this document covers most of the science regarding the holothurian FucCS. Both structural and medical properties of this unique GAG, investigated during the last 25 years, are systematically discussed herein.

Discovery of an intrinsic tenase complex inhibitor: Pure nonasaccharide from fucosylated glycosaminoglycan

“…Discussion FG, a novel glycosaminoglycan derivate from sea cucumber, is markedly different from typical mammalian glycosaminoglycans, such as dermatan sulfate and chondroitin sulfate, because of its unique sulfated fucose side chains, although it possesses a chondroitin sulfate-like backbone (31). In recent years, FG has attracted increasing attention from researchers because of its high yields (∼1%) from the dried body wall of sea cucumber and because of its biological activities, including anticoagulant, antithrombotic, anticancer, and anti-HIV activities (14,(31)(32)(33). Over the past 30 y, the basic structure of FG has been studied using chemical methods such as desulfation, defucosylation, and methylation together with NMR analyses and analyses of the products formed by digesting the partially defucosylated chondroitin sulfate with chondroitinase AC or ABC (20)(21)(22).…”

“…For over 30 y since its discovery the detailed structures of native FG and its depolymerized products have not been elucidated, because these polysaccharides are heterogeneous, namely they are mixtures of isomers with different molecular weights, and because limitations exist in the available strategies for analyzing such molecules (17,20). For example, although it is assumed that a single fucose (Fuc) is linked to the C-3 position of glucuronic acid (GlcA) via an α-glycosidic bond, there is no direct evidence excluding the possibility that Fuc may be linked to the C-4 and C-6 positions of N-acetylgalactosamine (GalNAc) and that the Fuc side chain may exist as a di-or trisaccharide side chain (14,(21)(22)(23)(24). Because the polydisperse and structurally ambiguous native FG and its illdefined depolymerized products are not suitable for the precise evaluation of their structure-activity relationships, in general, the purification of FG-derived fragments is crucial for probing these structure-activity relationships with regard to the inhibition of the intrinsic tenase and for elucidating the detailed structure of FG.…”

“…1), which is a complex acidic polysaccharide isolated from sea cucumber, has recently attracted considerable attention because of its various bioactivities (14). Notably, FG has potent anticoagulant and antithrombotic activities due to its inhibition of the intrinsic tenase (15)(16)(17).…”

Inhibition of thrombin generation by dermatan sulfate isolated from the skin of Oreochromis niloticus

“…GAGs comprise a variable family of highly complex glycans produced from vertebrate and invertebrate tissues (Volpi & Maccari, 2002;Arima et al, 2013;Pomin, 2014;Sayan et al, 2016). They are heteropolysaccharides consisting of repeated units of alternating residues of N-acetylgalactosamine or glycosamine linked to a non-nitrogenated sugar, like uronic acid (D-glycuronic acid or L-iduronic acid) or a galactose, making themselves typical chains are known as mucopolysaccharides, and their association to proteoglycans form the matrix' principal elements playing several physiological and pathological events (Tovar et al, 2005;Volpi, 2011;Oliveira et al, 2015).…”

Tributylamine Facilitated Separations of Fucosylated Chondroitin Sulfate (Fucs) by High Performance Liquid Chromatography (HPLC) into its Component Using 1-Phenyl-3-Methyl- 5-Pyrazolone (PMP) Derivatization

“…The mucopolysaccharide consists of a common chondroitin sulfate chain with the β-D-glucuronic acid moiety O-substituted with sulfated fucosyl at the carbon-3 position [2]. The hydrolysis sequence of this mucopolysccharide into its component starts by removal of sulfate esters at the vicinity of fucose branch followed by fucose release and sulfates in the chondroitin backbone.…”