...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemistry >DNA Aptamers to Thrombin Exosite I. Structure-Function Relationships and Antithrombotic Effects
【24h】

DNA Aptamers to Thrombin Exosite I. Structure-Function Relationships and Antithrombotic Effects

机译：DNA适体到凝血酶exosite I.结构功能关系和抗血栓形成

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

DNA aptamers (oligonucleotides) interacting with thrombin exosite I contain G-quadruplex, two T-T, and one T-G-T loops in their structure. They prevent exosite I binding with fibrinogen and thrombin receptors on platelet surface, thereby suppressing thrombin-stimulated formation of fibrin from fibrinogen and platelet aggregation. Earlier, we synthe-sized original antithrombin aptamer RE31 (5'-GTGACGTAGGTTGGTGTGGTTGGGGCGTCAC-3') that contained (in addition to G-quadruplex) a hinge region connected to six pairs of complementary bases (duplex region). In this study, we compared properties of RE31 aptamer and its analogues containing varying number of bases in the duplex region and nucleotide insertions in the hinge region. Reduction in the number of nucleotides in the duplex region by 1 to 4 pairs (in comparison with RE31 aptamer) resulted in the decrease of the structural stability of aptamers (manifested as lower melting temperatures) and their ability to inhibit thrombin-stimulated fibrin formation in human blood plasma in tests of thrombin, prothrombin, and activated partial thromboplastin times. However, an increase in the number of bases by 1 to 2 pairs did not cause significant changes in the stability and antithrombin activity of the aptamers. Insertions into the hinge region of RE31 aptamer decreased its antithrombin activity. Investigation of RE31 antithrombotic properties demonstrated that RE31 (i) slowed down thrombin formation in human blood plasma (thrombin generation test), (ii) accelerated lysis of fibrin clot by tissue plasminogen activator in in vitro model, and (iii) suppressed arterial thrombosis in in vivo model. Based on the obtained data, RE31 aptamer can be considered as a potentially effective antithrombotic compound.
机译：与凝血酶外，I含有G-Quadrepled，两种T-T和其结构中的一个T-G-T环的DNA适体（寡核苷酸）。它们可防止血小板表面上与纤维蛋白原和凝血酶受体结合，从而抑制来自纤维蛋白原和血小板聚集的凝血酶刺激的纤维蛋白的形成。早些时候，我们合成的原始抗凝血酶Aptamer Re31（除了G-Quadruplex）之外的铰链区域（除G-quadruplex）附属于六对互补底座（双工区域）的铰链区域。在该研究中，我们比较了Re31适体的特性及其在双相区域中含有不同数量的碱基和铰链区域中的核苷酸插入的性能。减少双相区域中的核苷酸的数量1至4对（与RE31适体相比）导致适体的结构稳定性（表现为较低的熔化温度）的结构稳定性及其抑制凝血酶刺激的纤维蛋白形成的能力人血浆在凝血酶，凝血酶凝血酶和活化的部分血栓形成时间的试验中。然而，碱基的增加1至2对的增加不会导致适体的稳定性和抗抗凝血酶活性的显着变化。插入RE31适体的铰链区域降低其抗凝血酶活性。 Re31抗血栓性能的研究证明，RE31（i）减缓了人血浆（凝血酶生成试验）中的凝血酶形成，（ii）通过组织纤溶酶原激活剂在体外模型中加速裂解纤维蛋白凝块，（III）抑制动脉血栓形成在体内模型中。基于所获得的数据，RE31适体可以被认为是潜在有效的抗血栓形成化合物。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号