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|Title:||Chemistry and Biology of Glycosaminoglycans in Blood Coagulation||Authors:||Barbucci, Rolando
|Keywords:||sulfated glycosaminoglycans; hyaluronic acid; anticoagulant activity; antithrombotic activity; antithrombin III; heparin cofactor II; thrombin; Factor Xa||Issue Date:||1996||Project:||None||Journal:||POLYMERS FOR ADVANCED TECHNOLOGIES||Abstract:||
Glycosaminoglycans (GAGS) are widely distributed in animal tissues where they are usually associated with proteins. Six types are commonly recognized: heparin (Hep), heparan sulfate (HS), dermatan sulfate ( D S ) , chondroitin sulfate (Ch-S), keratan sulfate ( K S ) and hyaluronic acid (Hyal). They are structurally related with a carbohydrate backbone consisting of alternating hex- uronic acid (L-iduronic acid andlor D-glucuronic acid) or galactose units and hexosamine (D-glucosamine or D- galactosarnine) residues. AIl GAGs, except Hyal, show sulfate groups along their chains. Certain sulfate glyco- aminoglycans have the ability to interfere with blood coagulation, as demonstrated by the extensive clinical use of Hep as an anticoagulant agent. HS and DS show a good anticoagulant activity, although weaker than that of Hep. In contrast, Ch-S has a low ability to inhibit plasma serine proteases, and KS and Hyal are devoid of any effect on coagulation cascade. The interaction between blood coagu- lation serine proteases and GAGS can be found to have two principle mechanisms: the specific "lock and key" binding and the nonspecific cooperative electrostatic association. This different ability of GAGs to interact with coagulation cascade proteins depends on the molecular weight, the ratio of iduroniclglucoronic acid and the sulfation degree. Many attempts have been made to improve or induce anticoagulant activity of natural GAGs by chemical modification. Increasing sulfation degree of DS and Ch-S is followed by their biological activity increasing. Hyal, which is devoid of any anticoagulant effect, acquires a good ability to inactivate plasma serine proteases, i.e. thrombin and Factor Xa, when it is sulfated. This ability increases by increasing the number of sulfate groups per disaccharide unit, although the mechanism of action is different from that of
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