Two Families of Synthetic Peptides That Enhance Fibrin Turbidity and Delay Fibrinolysis by Different Mechanisms
Two Families of Synthetic Peptides That Enhance Fibrin Turbidity and Delay Fibrinolysis by Different Mechanisms
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DOI：
10.1021/bi900647g
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发表时间：
2009-08-04
期刊：
影响因子：
2.9
通讯作者：
Doolittle, Russell F.
中科院分区：
文献类型：
--
作者：
Pandi, Leela;Kollman, Justin M.;Doolittle, Russell F.
当在某些带正电荷的肽存在下在体外形成纤维蛋白凝块时，浊度增强并且纤维蛋白溶解延迟。在这里，我们表明，这两种现象并不总是联系在一起，不同的家庭的肽带来的延迟裂解以不同的方式。在对应于纤维蛋白原γ C和β C结构域的某些区域的固有粘附肽的情况下，即使这些肽与纤维蛋白（原）结合并增强浊度，溶解的延迟主要是由于直接抑制纤溶酶原活化。相反，对于在纤维蛋白B结上形成图案的某些五肽，溶解延迟是纤维蛋白单元如何组装的结果。这些B结替代物本身可以诱导纤维蛋白原分子的凝胶化。通过与GHRPYam共结晶的来自人纤维蛋白原的D-二聚体的晶体结构揭示了凝块浊度增加和纤维蛋白溶解延迟的可能原因，其包装显示配体酪氨酸直接参与反平行β C-β C相互作用。
When fibrin clots are formed in vitro in the presence of certain positively charged peptides, the turbidity is enhanced and fibrinolysis is delayed. Here we show that these two phenomena are not always linked and that different families of peptides bring about the delay of lysis in different ways. In the case of intrinsically adhesive peptides corresponding to certain regions of the fibrinogen gamma C and beta C domains, even though these peptides bind to fibrin(ogen) and enhance turbidity, the delay in lysis is mainly due to direct inhibition of plasminogen activation. In contrast, for certain pentapeptides patterned on Fibrin B knobs, the delay in lysis is a consequence of how fibrin units assemble. On their own, these B knob surrogates can induce the gelation of fibrinogen molecules. The likely cause of enhanced clot turbidity and delay in fibrinolysis was revealed by a crystal structure of the D-dimer from human fibrinogen cocrystallized with GHRPYam, the packing of which showed the direct involvement of the ligand tyrosines in antiparallel beta C-beta C interactions.