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Heparan sulfate analogue
Heparan sulfate analogues are polymers engineered to mimic several properties of heparan sulfates.〔 They can be constituted with a backbone of polysaccharides, such as poly glucose or glucuronates〔Petit et al, Controlled sulfatation of natural anionic bacterial polysaccharides can yield agents with specific regenerating activity in vivo. Biomacromolecules 2004;5:445-52〕 or a polyester such as co polymers of lactic or malic acid〔Jeanbat-Mimaud et al, Bioactive functionalized polymer of malic acid for bone repair and muscle regeneration. J Biomater Sci Polym Ed. 2000;11(9):979-91.〕 to which sulfates, sulfonate or carboxylgroups are added in controlled amounts and location. They have a molecular weight that can range from a few thousands to several hundred thousand Dalton.
Heparan sulfates can sequester growth factors (GFs) and cytokines in the extracellular matrix (ECM) thereby protecting them from degradation. This ensures local presence of these signaling proteins to fulfill their function in the ECM which contributes to the preservation of anatomical form and function.〔 Heparan sulfates bind to matrix proteins on specific sites called "heparan sulfate binding sites" on ECM macromolecules like collagen, fibronectin and laminin, to form a scaffold surrounding the cells and to protect ECM proteins and growth factors from proteolytic degradation by steric hindrance. However, at any site of inflammation, so also in wound areas, heparan sulfates are degraded, mainly by heparanases〔〔〔Barbier-Chassefière et al, Matrix therapy in regenerative medicine, a new approach to chronic wound healing. J Biomed Mater Res A. 2009 Sep 1;90(3):641-7.〕〔 giving free access to protease to degrade the ECM and a subsequent loss of GFs and cytokines that disrupts the normal tissue homeostasis.〔〔〔〔 Heparan sulfate analogues obtain many of the characteristics of heparan sulfates including the ability to sequester GFs and bind and protect matrix proteins.〔〔Morvan et al, An engineered biopolymer prevents mucositis induced by 5-fluorouracil in hamsters. Am J Pathol. 2004;164(2);739-46.〕 However, heparan sulfate analogues are resistant to enzymatic degradation.〔〔 This way they strengthen the healing potential of the wound bed by repositioning GFs and cytokines back into the ECM.〔〔〔〔
== Heparan sulfate analogues ==
Several Heparan sulfate analogues (also known as ReGeneraTing Agents, RGTA) have been developed from a poly glucose backbone. One named OTR4120 is a 85KD biopolymer and used for topical or ophthalmological application and marketed under the name CACIPLIQ20 or CACICOL20, respectively.〔(【引用サイトリンク】title=OTR3 )〕 Heparan sulfate analogues will occupy the free heparan sulfate binding sites on ECM macromolecules like collagen, fibronectin and laminin that become available following heparan sulfate degradation.
In many characteristics heparan sulfate analogues are similar to the natural heparan sulfate.〔〔Barritault et al, Regenerating agents (RGTAs): a new therapeutic approach. Ann Pharm Fr. 2006 Mar;64(2):135-44.〕 The most important difference is their resistance to enzymatic degradation.〔〔〔 The resistance of RGTA is caused by the coupling of the subunits internal bond of the molecules. The β2-4 carbon-carbon binding of the subunits of heparan sulfate is prone to enzymatic cleavage whereas the α1-6 carbon-carbon binding of the subunits of heparan sulfate analogues are resistant to cleavage by all known mammalian glycanases and heparanases.〔〔〔〔〔〔〔 This way RGTA can recreate a scaffold with the ECM proteins and will reposition GFs back into the matrix where they can re-unfold their natural action in wound repair. This way heparan sulfate analogues may contribute to chronic wound healing as will be discussed later on.
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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