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

Barbucci, R., Magnani, A., Lamponi, S., Albanese, A. (1996). Chemistry and Biology of Glycosaminoglycans in Blood Coagulation. POLYMERS FOR ADVANCED TECHNOLOGIES, 7(8), 675-685.

Chemistry and Biology of Glycosaminoglycans in Blood Coagulation

BARBUCCI, ROLANDO;MAGNANI, AGNESE;LAMPONI, STEFANIA;ALBANESE, ANTONIETTA
1996-01-01

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
Barbucci, R., Magnani, A., Lamponi, S., Albanese, A. (1996). Chemistry and Biology of Glycosaminoglycans in Blood Coagulation. POLYMERS FOR ADVANCED TECHNOLOGIES, 7(8), 675-685.
File in questo prodotto:
File Dimensione Formato  
pol advanc technol 1996.pdf

non disponibili

Tipologia: Post-print
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 863.85 kB
Formato Adobe PDF
863.85 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/40504
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo