Structural requirements of heparin disaccharides responsible for hemorrhage: reversion of the antihemostatic effect by ATP.
Topically applied heparin and heparan sulfate disaccharides, with the basic structure delta-4,5 uronyl-(1----4)-glucosamine and bearing a sulfate at the C-6 position of the glucosamine residue, are antihemostatics as potent as heparin, producing uncontrollable hemorrhage from small blood vessels. The finding that other sulfated disaccharides with the same sulfate:hexosamine:uronic acid ratios but with the sulfate at a different position (C-2), or with different glycosidic linkage (1----3), were inactive as inhibitors of hemostasis indicates that a specific structure is needed to produce the effect. The inhibitory activity of the normal hemostatic process could be reversed by ATP. Molecular models show that part of the disaccharide inhibitors and ATP hold a similar structural conformation.
Nader
H B
HB
Departamento de Bioquímica, Escola Paulista de Medicina, Säo Paulo, Brazil.
Tersariol
I L
IL
Dietrich
C P
CP
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D004187:Disaccharides / Q000009:adverse effects*; D006025:Glycosaminoglycans / Q000009:adverse effects*; D006470:Hemorrhage / Q000139:chemically induced*; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000009:adverse effects*; D006497:Heparan Sulfate / Q000009:adverse effects*; D013329:Structure-Activity Relationship
D000255:Adenosine Triphosphate; D004187:Disaccharides; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate