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Molecules 2016, 21(2), 202;

Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures

Department of Materials Science and Engineering, College of Engineering, North Carolina State University, Raleigh, NC 27695, USA
Department of Molecular and Structural Biochemistry, College of Agriculture and Life Sciences, North Carolina State University, Raleigh, NC 27695, USA
Present address: Department of Chemistry, College of Science, Marshall University, Huntington, WV 25755, USA.
Author to whom correspondence should be addressed.
Received: 11 December 2015 / Accepted: 3 February 2016 / Published: 6 February 2016
(This article belongs to the Special Issue Thrombin Inhibitors: Discovery and Design)
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The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy reported for these aptamers during clinical trials, multiple aptamers have been linked using DNA nanostructures. Here, we modify that strategy by linking multiple copies of various thrombin-binding aptamers using DNA weave tiles. The resulting constructs have very high anticoagulant activity in functional assays owing to their improved cooperative binding affinity to thrombin due to optimized spacing, orientation, and the high local concentration of aptamers. We also report the results of molecular dynamics simulations to gain insight into the solution conformations of the tiles. Moreover, by using DNA strand displacement, we were able to turn the coagulation cascade off and on as desired, thereby enabling significantly better control over blood coagulation. View Full-Text
Keywords: thrombin; DNA aptamers; anticoagulation; DNA nanotechnology thrombin; DNA aptamers; anticoagulation; DNA nanotechnology

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Rangnekar, A.; Nash, J.A.; Goodfred, B.; Yingling, Y.G.; LaBean, T.H. Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures. Molecules 2016, 21, 202.

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