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肝素的结构特征及其对肝素辅因子II介导的凝血酶抑制作用的影响。

Structural features of heparin and their effect on heparin cofactor II mediated inhibition of thrombin.

作者信息

Kim Y S, Linhardt R J

机构信息

Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City 52242.

出版信息

Thromb Res. 1989 Jan 1;53(1):55-71. doi: 10.1016/0049-3848(89)90115-1.

DOI:10.1016/0049-3848(89)90115-1
PMID:2922702
Abstract

Heparins from different species and tissues show similar levels of ATIII and HCII mediated anti-IIa activities. On fractionation, chains containing predominantly ATIII or HCII activities could not be separated. Oligosaccharide mapping demonstrates that the concentration of an oligosaccharide comprising a portion of heparin's ATIII binding site in a particular heparin fraction correlates with ATIII mediated anti-IIa activity, but does not correlate with HCII mediated anti-IIa activity. These results suggest that ATIII and HCII do not share a common binding site. Partial enzymatic depolymerization of heparin resulted in large oligosaccharides which could be purified and partially characterized. Although oligosaccharides of degree of polymerization (dp) 18 and 20 showed significant ATIII and HCII mediated anti-IIa activities no separation of these activities resulted. These data suggest however that a minimum chain length of dp18 was required for HCII mediated anti-IIa activity.

摘要

来自不同物种和组织的肝素显示出相似水平的由抗凝血酶III(ATIII)和肝素辅因子II(HCII)介导的抗凝血酶IIa(anti-IIa)活性。在分级分离时,无法分离出主要含有ATIII或HCII活性的链。寡糖图谱分析表明,在特定肝素组分中,包含肝素ATIII结合位点一部分的寡糖浓度与ATIII介导的anti-IIa活性相关,但与HCII介导的anti-IIa活性无关。这些结果表明,ATIII和HCII不共享共同的结合位点。肝素的部分酶促解聚产生了可以纯化并部分表征的大寡糖。尽管聚合度(dp)为18和20的寡糖显示出显著的由ATIII和HCII介导的anti-IIa活性,但这些活性并未分离。然而,这些数据表明,HCII介导的anti-IIa活性需要dp18的最小链长。

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