微分作用的肝素和硫酸乙酰肝素与selectins葡糖氨基葡聚糖。影响使用未分离和低分子量肝素治疗药物。

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林哈特Koenig, Norgard-Sumnicht K, R, Varki

微分作用的肝素和硫酸乙酰肝素与selectins葡糖氨基葡聚糖。影响使用未分离和低分子量肝素治疗药物。

中国投资。1998年2月15日,101 (4):877 - 89。

PubMed ID

9466983 (在PubMed

]

文摘

selectins是calcium-dependent c型凝集素结合某些sialylated fucosylated,硫酸糖蛋白配体。L-selectin也承认内皮蛋白聚糖calcium-dependent的方式,通过硫酸乙酰肝素(HS)粘多糖链富含未被取代的氨基葡萄糖单位。我们现在表明,这些商品链还可以绑定P-selectin,但不是E-selectin。然而,尽管L-selectin绑定需要微摩尔的级别的自由钙,P-selectin识别在很大程度上是二阶cation-independent。尽管如此,商品链绑定到P-selectin筛选了由乙二胺四乙酸(EDTA),但只有在高浓度。猪肠道粘膜(肥大细胞衍生)肝素(PIM-heparin)显示类似的属性,没有绑定到E-selectin, calcium-dependent绑定的一个小分支L-selectin P-selectin, P-selectin和calcium-independent绑定一个更大的一部分,后者被EDTA浓度高而中断。分析肝素定义片段池显示了交互作用的大小依赖,tetradecasaccharides显示很容易被绑定到L -和P-selectin亲和力列。L-selectin绑定片段包括硫酸和epimerized地区更大,与内皮商品链,它们丰富自由氨基酸组。P-selectin绑定组件包括这个分数以及一些不太高度修改过的区域。因此,endothelium-derived商品链和肥大细胞衍生肝素可以扮演一个角色在调制selectins体内的生物学。 Notably, P- and L-selectin binding to sialyl-Lewisx and to HL-60 cells (which are known to carry the native ligand PSGL-1) is inhibited by unfractionated pharmaceutical heparin preparations at concentrations 12-50-fold lower than those recommended for effective anticoagulation in vivo. In contrast, two low molecular weight heparins currently considered as clinical replacements for unfractionated heparin are much poorer inhibitors. Thus, patients undergoing heparin therapy for other reasons may be experiencing clinically significant inhibition of L- and P-selectin function, and the current switchover to low-molecular weight heparins may come at some loss of this effect. Low-dose unfractionated heparin should be investigated as a treatment option for acute and chronic diseases in which P- and L-selectin play pathological roles.

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药物靶点

药物	目标	类	生物	药理作用	行动
肝素钠	P-selectin	蛋白质	人类	未知的	抑制剂	细节