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排序方式: 共有106条查询结果,搜索用时 0 毫秒
1.
E. Manseth P.O. Skjervold S.O. Flera F.R. Brosstad O.R. Ødegaard R. Flengsrud 《Journal of food science》2003,68(5):1648-1652
Thrombin from Atlantic salmon (Salmo salar) was purified and characterized as a potential new binding agent for the food industry. Purification was performed avoiding inhibitors, using BaSO4 adsorption and heparin‐Sepharose affinity chromatography. Prothrombin activation was performed using a mixture of eggs and gills from salmon. Optimized conditions for the adsorption, elution, and the activation step are presented. The purified thrombin clotted bovine fibrinogen with a specific activity of 1423 U/mg. Sequence data are presented and compared with other species. This method of nontoxic activation and purification will allow salmon thrombin to be used in the food industry. 相似文献
2.
Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with a 5-year survival rate of less than 10% following diagnosis. The aggressive and invasive properties of pancreatic cancer tumors coupled with poor diagnostic options contribute to the high mortality rate since most patients present with late-stage disease. Accordingly, PDAC is linked to the highest rate of cancer-associated venous thromboembolic disease of all solid tumor malignancies. However, in addition to promoting clot formation, recent studies suggest that the coagulation system in PDAC mediates a reciprocal relationship, whereby coagulation proteases and receptors promote PDAC tumor progression and dissemination. Here, upregulation of tissue factor (TF) by tumor cells can drive local generation of the central coagulation protease thrombin that promotes cell signaling activity through protease-activated receptors (PARs) expressed by both tumor cells and multiple stromal cell subsets. Moreover, the TF-thrombin-PAR1 signaling axis appears to be a major mechanism of cancer progression in general and PDAC in particular. Here, we summarize the current literature regarding the role of PAR1 in PDAC and review possibilities for pharmacologically targeting PAR1 as a PDAC therapeutic approach. 相似文献
3.
免标记DNA电化学传感器测定凝血酶 总被引:2,自引:2,他引:0
研制了一种基于介孔二氧化硅负载纳米金和适体DNA的免标记电化学传感器,用于检测凝血酶的含量。实验中先用三甲基氯硅烷(TMCS)封闭介孔二氧化硅(MPS)前驱体外壁硅羟基的活性,煅烧除去模板剂后,再用氨基丙基三乙氧基硅烷(APTS)与孔道内壁硅羟基反应,接枝氨基,最后得到内壁修饰氨基的介孔硅材料(APTS-TMCS-MPS)。金纳米粒子(GNPs)通过与APTS-TMCS-MPS氨基的静电作用力组装到介孔孔道内,然后和巯基修饰的适体DNA通过金硫键相结合,制得免标记探针(DNA/GNPs/APTSTMCS-MPS)。将探针修饰在玻碳电极表面,制得免标记DNA电化学传感器。将该传感器与含有凝血酶的待测液温育反应后,凝血酶和固定在介孔内的适体DNA发生特异性反应,形成位阻较大的适体DNA和凝血酶的复合物,从而增加了介孔孔道内的空间位阻,导致电流响应信号降低。随着凝血酶浓度的增加,孔道内部的位阻也随之增加。根据形成的复合物对电子转移和响应电流的阻碍,可以实现对凝血酶的免标记测定。实验结果表明,APTS-TMCS-MPS介孔孔道内的GNPs,可以提高孔道内电子的传递效率。在优化的实验条件下,该免标记DNA电化学传感器对凝血酶的检测线性范围是1.0×10-8~1.0×10-6 mol·L-1,检测限是7.5×10-9 mol·L-1(3σ)。 相似文献
4.
Jinmi Zou Frauke Swieringa Bas de Laat Philip G. de Groot Mark Roest Johan W. M. Heemskerk 《International journal of molecular sciences》2022,23(20)
Integrin αIIbβ3 activation is essential for platelet aggregation and, accordingly, for hemostasis and arterial thrombosis. The αIIbβ3 integrin is highly expressed on platelets and requires an activation step for binding to fibrinogen, fibrin or von Willebrand factor (VWF). A current model assumes that the process of integrin activation relies on actomyosin force-dependent molecular changes from a bent-closed and extended-closed to an extended-open conformation. In this paper we review the pathways that point to a functional reversibility of platelet αIIbβ3 activation and transient aggregation. Furthermore, we refer to mouse models indicating that genetic defects that lead to reversible platelet aggregation can also cause instable thrombus formation. We discuss the platelet agonists and signaling pathways that lead to a transient binding of ligands to integrin αIIbβ3. Our analysis points to the (autocrine) ADP P2Y1 and P2Y12 receptor signaling via phosphoinositide 3-kinases and Akt as principal pathways linked to reversible integrin activation. Downstream signaling events by protein kinase C, CalDAG-GEFI and Rap1b have not been linked to transient integrin activation. Insight into the functional reversibility of integrin activation pathways will help to better understand the effects of antiplatelet agents. 相似文献
5.
6.
Su Z Vinogradova A Koutychenko A Tolkatchev D Ni F 《Protein engineering, design & selection : PEDS》2004,17(8):647-657
The tetrapeptide Phe-Asn-Pro-Arg is a structurally optimized sequence for binding to the active site of thrombin. By conjugating this tetrapeptide or some variants to a C-terminal fragment of hirudin, we were able to generate a series of new bivalent inhibitors of thrombin containing only genetically encodable natural amino acids. We found that synergistic binding to both the active site and an exosite of thrombin can be enhanced through substitutions of amino acid residues at the P3 and P3' sites of the active-site directed sequence, Phe(P4)-Xaa(P3)-Pro(P2)-Arg(P1)-Pro(P1')-Gln(P2')-Yaa(P3'). Complementary to rational design, a phage library was constructed to explore further the residue requirements at the P4, P3 and P3' sites for bivalent and optimized two-site binding. Very significantly, panning of the phage library has led to thrombin-inhibitory peptides possessing strong anti-clotting activities in the low nanomolar range and yet interfering only partially the catalytic active site of thrombin. Modes of action of the newly discovered bivalent inhibitors are rationalized in light of the allosteric properties of thrombin, especially the interplay between the proteolytic action and regulatory binding occurring at thrombin surfaces remote from the catalytic active site. 相似文献
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8.
Prof. Dr. Torsten Steinmetzer Dr. Bernhard Baum Dr. Adam Biela Prof. Dr. Gerhard Klebe Prof. Dr. Götz Nowak Dr. Elke Bucha 《ChemMedChem》2012,7(11):1965-1973
During extracorporeal circulation, when blood comes in contact with artificial surfaces, patients receive a standard treatment with anticoagulants to avoid blood coagulation. Dialysis patients in particular are systemically treated with heparin up to four times a week, causing a high burden for the body. For potential anticoagulant modification of external materials, such as dialysis equipment, a series of highly potent thrombin inhibitors was developed. All inhibitors share the general formula arylsulfonyl‐P3‐Pro‐4‐amidinobenzylamide, where P3 is glycyl or a trifunctional amino acid residue in L ‐configuration. Among this series, several derivatives inhibit thrombin with Ki values of less than 1 nM . Specificity measurements revealed that this inhibitor type is highly specific for thrombin with negligible activity against related trypsin‐like serine proteases. X‐ray analysis of the most potent analogue in complex with thrombin demonstrated that the N‐terminal arylsulfonyl group occupies the aryl binding site, whereas the P3 side chain is directed into the solvent and therefore is well suited for further coupling. Based on their in vitro profile, these inhibitors are suitable candidates for the development of hemocompatible materials with anticoagulant properties. 相似文献
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10.
Thrombolytic Agents: Thrombosis‐Responsive Thrombolytic Coating Based on Thrombin‐Degradable Tissue Plasminogen Activator (t‐PA) Nanocapsules (Adv. Funct. Mater. 45/2017) 下载免费PDF全文