Programming Hybrid Aptamers on Graphene Oxide to Efficiently Inhibit the Activity of Thrombin

• Main Authors: Lin, Ting-Xuan, 林亭瑄
• Other Authors: Huang, Chih-Ching
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/64qvt3

碩士 === 國立臺灣海洋大學 === 生命科學暨生物科技學系 === 106 === In this work, we demonstrated a strategy to target exosites I and II of thrombin simultaneously by using programmed hybrid-aptamers for enhanced anticoagulation efficiency. The targeting ligand is denoted as Supra-TBA15/29 (Supramolecular TBA15/29), containing TBA15 (15-base, binding to the exosite I of thrombin), TBA29 (29-base, binding to the exosite II of thrombin) and is designed to allow hybridization and linking of different aptamers to form a chain of TBAs. The programmed hybrid-aptamers (Supra-TBA15/29) were immobilized on graphene oxide (GO) to further boost the anticoagulation activity. The Supra-TBA15/29 modified on GO (~230 nm) forms Supra-TBA15/29GO strand mainly through van der Waals’ force, ππ stacking and hydrogen-bonding between poly(adenine) (from Supra-TBA15/29) and GO. The Supra-TBA15/29 on GO had optimal distances between TBA15 and TBA29 units, aptamer density, and desired orientation on the GO surfaces, which enhanced the interaction between Supra-TBA15/29–GO and thrombin, resulting in high anticoagulant potency. The dose-dependent thrombin clotting time (TCT) delay caused by Supra-TBA15/29–GO is >3 times longer than that of four commercially available drugs (heparin, argatroban, hirudin or warfarin). Herein, we demonstrated that Supra-TBA15/29–GO are highly stable (half-life >2 days in the human plasma) and biocompatible (low cytotoxicity and hemolysis) with a great potential for treatment of hemostatic disorders.