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首页> 外文期刊>Chemistry: A European journal >Highly efficient control of thrombin activity by multivalent nanoparticles
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Highly efficient control of thrombin activity by multivalent nanoparticles

机译：多价纳米颗粒对凝血酶活性的高效控制

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We have demonstrated that the incorporation of sulfated galactose acid (sulf-Gal) into thrombin-binding-aptamer (TBA)-conjugated gold nanoparticles (TBA-AuNPs) enables highly effective inhibition of thrombin activity toward fibrinogen. AuNP bioconjugates (TBA_(15)/TBA_(29)/sulf-Gal- AuNPs) were prepared from 13 nm AuNPs, 15-mer thrombin-binding aptamer (TBA _(15)), 29-mer thrombin-binding aptamer (TBA_(29)), and sulf-Gal. The numbers of TBA and sulf-Gal molecules per AuNP proved to have a strong impact on inhibitory potency. The best results were observed for 15-TBA_(15)/TBA_(29)/sulf-Gal-AuNPs (with 15 TBA_(15) and 15 TBA_(29) molecules per AuNP), which, because of their particularly flexible conformation and multivalency, exhibited ultrahigh binding affinity toward thrombin (K_d=3.4?-10~(-12) M) and thus extremely high anticoagulant (inhibitory) potency. Compared to the case without inhibitors (the "normal" value), their measured thrombin clotting time (TCT) was 91 times longer, whereas for TBA_(15) alone it was only 7.2 times longer. Their anticoagulant activity was suppressed by TBA-complementary-sequence (cTBA)-modified AuNPs (cTBA_(15)/cTBA _(29)-AuNPs) at a rate that was 20 times faster than that of free cTBA15/cTBA29. Thus, easily prepared, low-cost, multivalent AuNPs show great potential for biomedical control of blood clotting.
机译：我们已经证明，将硫酸化的半乳糖酸（sulf-Gal）掺入凝血酶结合适体（TBA）结合的金纳米颗粒（TBA-AuNPs）中，可以高度有效地抑制凝血酶对纤维蛋白原的活性。由13 nm AuNP，15-mer凝血酶结合适体（TBA_（15）），29-merthromb-binding aptamer（TBA_）制备AuNP生物共轭物（TBA_（15）/ TBA_（29）/ sulf-Gal-AuNP） （29））和硫代Gal。每个AuNP的TBA和硫-Gal分子数量证明对抑制效能有很大影响。对于15-TBA_（15）/ TBA_（29）/ sulf-Gal-AuNPs（每个AuNP具有15个TBA_（15）和15个TBA_（29）分子）观察到了最佳结果，这是由于它们特别灵活的构象和多价，表现出对凝血酶的超高结合亲和力（K_d = 3.4？-10〜（-12）M），因此具有极高的抗凝（抑制）效能。与没有抑制剂的情况相比（“正常”值），他们测得的凝血酶凝血时间（TCT）长91倍，而仅TBA_（15）仅长7.2倍。它们的抗凝血活性被TBA互补序列（cTBA）修饰的AuNPs（cTBA_（15）/ cTBA _（29）-AuNPs）抑制，其速率比游离cTBA15 / cTBA29快20倍。因此，易于制备，低成本，多价的AuNPs在血液凝结的生物医学控制方面显示出巨大的潜力。

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