Mechanism of potentiation of antithrombin III [at-III]inhibition by sulfated xylans

• Published in: Thrombosis research Vol. 47; no. 3; pp. 341 - 352
• Main Authors: Campbell, A., Nesheim, M.E., Doctor, V.M.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 01.08.1987; Elsevier Science
• Subjects: anticoagulant; Anticoagulants; Antithrombin III - pharmacology; Biological and medical sciences; Blood Coagulation Tests; Blood. Blood coagulation. Reticuloendothelial system; Drug Synergism; Edible Grain - analysis; Factor X - antagonists & inhibitors; Factor Xa; heparin; Heparin - pharmacology; Humans; Medical sciences; Molecular Weight; Pentosan Sulfuric Polyester - pharmacology; Pharmacology. Drug treatments; Polysaccharides - pharmacology; Prothrombin - antagonists & inhibitors; SP-54; Sulfated xylan; Sulfates - pharmacology; Wood; Xylans - isolation & purification; Xylans - pharmacology; Zea mays - analysis; Sulfated xylan; heparin; SP-54; anticoagulant; Potentiation; Inhibition; Mechanism of action; Antithrombin III
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(87)90148-4

Anticoagulant properties of three sulfated compounds prepared from xylans isolated from corn cobs, larchwood and oatspelts were compared with heparin and sodium pentosan polysulfate (SP-54) by studying their effects on activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using pooled normal human plasma. These compounds were more effective than SP-54 in delaying coagulation by all the three procedures while oatspelts xylan sulfate was as effective as heparin in inhibiting APTT and PT and more effective than heparin in inhibiting TT on a molar basis. The sulfated xylans were more effective than heparin or SP-54 in potentiating the AT-III inhibition of amidolysis of H-D-Phe-Pip-Arg-pNa (S-2238) by thrombin (IIa) or amidolysis of Bz-Ile-Glu-Gly-Arg-pNa (S-2222) by Xa. Study of the high affinity binding of the xylan sulfates to AT-III-Sepharose column showed that the amount of the xylan sulfate recovered in the eluates from this peak was greatly increased with an increase in molecular weight (MW). A buffered mixture of IIa, AT-III and dansylarginine N-(3-ethyl-1,5-pentanediyl) amide (DAPA) was used to study the inactivation of IIa by AT-III. Larchwood xylan sulfate (2–10 μg) was found to accelerate this inactivation which was neutralized by human platelet factor 4(PF 4). The results also suggested an interaction between larchwood xylan sulfate and IIa which may potentiate an interaction between AT-III and IIa.