Danishefsky I, Ahrens M, Klein S
Biochim Biophys Acta. 1977 Jun 23;498(1):215-22. doi: 10.1016/0304-4165(77)90101-5.
Studies were conducted to determine the effect of modifying specific functional groups of heparin on its antithrombin III-enhancing activity. The derivatives employed were heparin methyl ester, heparinylglycine and N-desulfated heparin. The carboxyl-modified derivatives increase the rate of inhibition of thrombin by antithrombin III, although not to the same extent as heparin. N-Desulfated heparin is devoid of any activity. Heparin methyl ester is more potent than heparinylglycine in activating antithrombin III, as exhibited by its immediate effect on the thrombin-fibrinogen reaction. However, heparinylglycine is the more effective of the two, in increasing the rate of thrombin deactivation by antithrombin III. The results indicate that although free carboxyl groups of heparin are not crucial for its binding to antithrombin III, they are important for the combination of the latter with thromobin. In contrast, N-sulfates are critical for the interaction of heparin with antithrombin III.
开展了多项研究以确定修饰肝素特定官能团对其增强抗凝血酶III活性的影响。所采用的衍生物为肝素甲酯、肝素基甘氨酸和N-去硫酸化肝素。羧基修饰的衍生物可提高抗凝血酶III对凝血酶的抑制速率，尽管程度不如肝素。N-去硫酸化肝素没有任何活性。肝素甲酯在激活抗凝血酶III方面比肝素基甘氨酸更有效，这体现在其对凝血酶-纤维蛋白原反应的即时作用上。然而，在提高抗凝血酶III使凝血酶失活的速率方面，肝素基甘氨酸是两者中更有效的。结果表明，尽管肝素的游离羧基对于其与抗凝血酶III的结合并非至关重要，但它们对于后者与凝血酶的结合很重要。相反，N-硫酸盐对于肝素与抗凝血酶III的相互作用至关重要。
