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Regulation of thrombin activity by ligand-induced topological alteration in a thrombin-binding aptamer
Shogo Sasaki1, Yue Ma2,3, Takatsugu Hirokawa4,5
1Department of Biotechnology and Life Science, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan. knaga@go.tuat.ac.jp.
Abstract:
Thrombin-binding aptamer (TBA), which forms a G-quadruplex (G4) structure with anti-parallel topology, interacts with thrombin to inhibit its enzymatic activity. Here we show that the G4-topology-altering ligand L2H2-2M2EA-6LCO (6LCO) changes the anti-parallel topology of TBA G4 to the parallel topology, thereby abrogating the thrombin-inhibitory activity of TBA. This finding suggests that G4 ligands that alter topology may be promising drug candidates for diseases involving G4-binding proteins.
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