Naggi A, Torri G, Casu B, Pangrazzi J, Abbadini M, Zametta M, Donati M B, Lansen J, Maffrand J P
Biochem Pharmacol. 1987 Jun 15;36(12):1895-900. doi: 10.1016/0006-2952(87)90485-0.
A new type of low-molecular-weight heparin (ss-LMW-H) was prepared (by controlled depolymerization and concurrent sulfation of heparin with a mixture of sulfuric and chlorosulfonic acid), to test the influence of extra-sulfate groups on biological properties of heparin fragments. The fragments had an average molecular weight ranging from 5000 to 10,000, a sulfate-to-carboxyl molar ratio of 2.8-3.1, and electrophoretic mobilities and NMR spectra distinctly different from those of the parent heparins. Depolymerization with oversulfation reduced the anticoagulant activity of heparin (ex vivo, in rats) much more than depolymerization alone, to about 10% of the original APTT and 25-30% of the original a.Xa units. By contrast, the antithrombotic activity (venous stasis model, in rats) was still comparable to that of heparin, and bleeding times were not significantly increased. The lipasemic (lipoprotein-lipase-releasing) activity of ss-LMW-H fragments was more than twice that of heparin. Results are discussed in terms of contribution of charge-density effects to different activities and to different mechanisms for the same activity of heparin.
通过用硫酸和氯磺酸混合物对肝素进行可控解聚和同时硫酸化，制备了一种新型低分子量肝素（ss-LMW-H），以测试额外硫酸基团对肝素片段生物学特性的影响。这些片段的平均分子量在5000至10,000之间，硫酸根与羧基的摩尔比为2.8 - 3.1，其电泳迁移率和核磁共振谱与母体肝素明显不同。过硫酸化解聚比单独解聚更能降低肝素（在大鼠体内）的抗凝活性，降至原始活化部分凝血活酶时间（APTT）的约10%和原始抗Xa单位的25 - 30%。相比之下，抗血栓活性（大鼠静脉淤滞模型）仍与肝素相当，且出血时间没有显著增加。ss-LMW-H片段的脂解（释放脂蛋白脂肪酶）活性是肝素的两倍多。从电荷密度效应对肝素不同活性以及相同活性的不同机制的贡献方面对结果进行了讨论。
