Micellar Thrombin-Binding Aptamers: Reversible Nanoscale Anticoagulants,Journal of the American Chemical Society

当前位置： X-MOL 学术 › J. Am. Chem. Soc. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Micellar Thrombin-Binding Aptamers: Reversible Nanoscale Anticoagulants
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2017-11-14 , DOI: 10.1021/jacs.7b07799
Alexander Roloff , Andrea S. Carlini , Cassandra E. Callmann , Nathan C. Gianneschi ₁

Affiliation

Aptamers are nucleic acid-based ligands that exhibit promising features including specific and reversible target binding and inhibition. Aptamers can function as anticoagulants if they are directed against enzymes of the coagulation cascade. However, they typically suffer from nucleolytic digestion and fast clearance from the bloodstream. We present thrombin-binding aptamer amphiphiles that self-assemble into nanoscale polymeric micelles with a densely functionalized aptamer-displaying corona. We show that these micellar aptamers retain their native secondary structure in a crowded environment and are stabilized against degradation by nucleases in human serum. Moreover, they are effective inhibitors of human plasma clotting in vitro. The inhibitory effect can be rapidly reversed by complementary nucleic acids that break the aptamers' secondary structure upon hybridization. Compared to free aptamers, the increased molecular weight and size of the overall assembly promotes extended blood circulation times in vivo.

中文翻译：

胶束凝血酶结合适体：可逆纳米级抗凝剂

适体是基于核酸的配体，其表现出有前途的特征，包括特异性和可逆的靶标结合和抑制。如果适体针对凝血级联的酶，则适体可用作抗凝血剂。然而，它们通常会受到溶核消化和血液中快速清除的影响。我们提出了凝血酶结合适体两亲物，它们自组装成纳米级聚合物胶束，具有密集功能化的适体展示电晕。我们表明，这些胶束适体在拥挤的环境中保留了它们的天然二级结构，并且在人血清中被核酸酶降解时保持稳定。此外，它们是体外人血浆凝固的有效抑制剂。破坏适体的互补核酸可以迅速逆转抑制作用。杂交后的二级结构。与游离适体相比，整体组装的分子量和大小的增加促进了体内血液循环时间的延长。

更新日期：2017-11-14

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南