硫酸化对一种与抗凝血酶III亲和力低的肝素组分的抗凝及抗凝血酶III结合特性的影响。

The effect of sulfation on the anticoagulant and antithrombin III-binding properties of a heparin fraction with low affinity for antithrombin III.

作者信息

Schoen P, Wielders S, Petitou M, Lindhout T

机构信息

Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.

出版信息

Thromb Res. 1990 Feb 1;57(3):415-23. doi: 10.1016/0049-3848(90)90257-d.

DOI:10.1016/0049-3848(90)90257-d

PMID:2315894

Abstract

Heparin with low affinity for antithrombin III (ATIII) and devoid of anticoagulant activity was chemically oversulfated and fractionated by affinity for ATIII. The oversulfated material showed ATIII binding properties, as monitored by intrinsic fluorescence enhancement of ATIII. The fluorescence increase was comparable to that of the AT III high affinity fraction of native heparin. The estimated dissociation constants however, showed a 10-fold weaker binding of the oversulfated material to ATIII, Kd = 6.4 x 10(-8) M, as compared to native heparin, Kd = 0.63 x 10(-8) M. Concomitant with the binding-induced allosteric change in ATIII, the oversulfated material stimulated the ATIII-thrombin and ATIII-factor Xa reactions. The high affinity fractions of native heparin and the sulfated material were almost equally effective in enhancing the rate of thrombin neutralization by ATIII. However, a 3-fold faster rate of factor Xa inactivation was found with the native high affinity material.

摘要

对抗凝血酶III（ATIII）亲和力低且无抗凝活性的肝素经化学过度硫酸化处理，并根据对ATIII的亲和力进行分级分离。通过ATIII的固有荧光增强监测发现，过度硫酸化的物质具有ATIII结合特性。荧光增加与天然肝素的AT III高亲和力级分相当。然而，与天然肝素（Kd = 0.63 x 10(-8) M）相比，过度硫酸化物质与ATIII的结合解离常数估计弱10倍，Kd = 6.4 x 10(-8) M。伴随着ATIII中结合诱导的变构变化，过度硫酸化物质刺激了ATIII-凝血酶和ATIII-因子Xa反应。天然肝素的高亲和力级分和硫酸化物质在增强ATIII中和凝血酶速率方面几乎同样有效。然而，发现天然高亲和力物质使因子Xa失活的速率快3倍。