A small fraction of dermatan sulfate with significantly increased anticoagulant activity was selected by interaction with the first complement protein.
Dermatan sulfate (DS) is a member of the family of structurally complex, sulfated, linear heteropolysaccharides called glycosaminoglycans (GAGs). It has a similar structure to heparin and heparan sulfate (HS), but with acetylgalactosamine replacing glucosamine, and the uronic acid moiety, mainly iduronic, joined 1-->3 to the hexosamine. We are studying the relationships between structure and activities of dermatan sulfate, in particular those associated with the thrombin inhibition mediated by heparin cofactor II (HCII). As we have demonstrated with heparin, a small fraction of dermatan sulfate was isolated by precipitation with the first component of the complement system, under very specific conditions of low ionic strength, and the presence of calcium ions. The sulfate content and the anticoagulant activity of the dermatan sulfate fraction isolated in the precipitate were three and four times greater respectively than the starting material. Our in vivo studies showed that this fraction has threefold higher thrombolytic activity than the DS. All these results suggest that this fraction could be used as a therapeutic agent for thrombi dissolution.
Calabrese
Graciela C
GC
Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, Ciudad Autónoma de Buenos Aires, 1113, Argentina. gcalabe@ffyb.uba.ar
Alberto
María F
MF
Tubio
Rosario
R
Marani
Mariela M
MM
Fernández De Recondo
Marta E
ME
Lazzari
María
M
Recondo
Eduardo F
EF
D000116:Acetylgalactosamine / Q000737:chemistry; D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000737:chemistry; D011232:Chemical Precipitation; D003172:Complement C1 / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006595:Hexosamines / Q000737:chemistry; D007067:Iduronic Acid / Q000737:chemistry; D008297:Male; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000737:chemistry
D000925:Anticoagulants; D003172:Complement C1; D005343:Fibrinolytic Agents; D006595:Hexosamines; D013431:Sulfates; D003871:Dermatan Sulfate; D007067:Iduronic Acid; D000116:Acetylgalactosamine; D002118:Calcium