Onoue Satomi, Harada Sunao, Nemoto Yoshitaka, Yajima Takehiko, Kashimoto Kazuhisa
Health Science Division, Itoham Foods, Inc., 1-2-1, Kubogaoka, Moriya, Ibaraki 302-0104, Japan.
Peptides. 2003 Jun;24(6):821-6. doi: 10.1016/s0196-9781(03)00171-2.
In the blood coagulation cascade, heparin activates human plasma antithrombin III (hAT III), resulting in the inhibition of factor Xa. This polysaccharide also exhibits hemorrhagic tendency mediated by the inhibition of thrombin in heparinotherapy. Therefore, attention has focused on the development of low molecular weight heparins (LMW-heparins) that inhibit factor Xa but not thrombin. In this investigation, we examined the biochemical and physicochemical properties of hAT III-derived heparin-binding peptides (HBPs). Of all the tested HBPs, hAT III (123-139) exhibited the highest affinity with heparin and showed an inhibitory effect on the heparin-induced enhancement of hAT III activity toward factor Xa, indicating that hAT III (123-139) specifically interacts with the active region in heparin. We prepared a synthetic hAT III (123-139)-coupled affinity chromatography system, and demonstrated that this novel affinity chromatography is useful for fractionation of highly active moieties in LMW-heparins.
在血液凝固级联反应中，肝素激活人血浆抗凝血酶III（hAT III），从而抑制因子Xa。在肝素治疗中，这种多糖还表现出因抑制凝血酶而介导的出血倾向。因此，注意力集中在开发抑制因子Xa但不抑制凝血酶的低分子量肝素（LMW-肝素）上。在本研究中，我们检测了hAT III衍生的肝素结合肽（HBP）的生化和物理化学性质。在所有测试的HBP中，hAT III（123-139）与肝素表现出最高的亲和力，并对肝素诱导的hAT III对因子Xa活性的增强具有抑制作用，表明hAT III（123-139）与肝素的活性区域特异性相互作用。我们制备了一种合成的hAT III（123-139）偶联亲和色谱系统，并证明这种新型亲和色谱可用于分离LMW-肝素中的高活性部分。
