Regulation of thrombin activity by ligand-induced topological alteration in a thrombin-binding aptamer
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 t...
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Published in | Chemical communications (Cambridge, England) Vol. 59; no. 57; pp. 8862 - 8865 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Royal Society of Chemistry
13.07.2023
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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.
The function of the thrombin-binding aptamer was regulated by the G-quadruplex topology-altering ligand of L2H2-2M2EA-
6LCO
, thereby controlling thrombin activity. |
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AbstractList | 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.
The function of the thrombin-binding aptamer was regulated by the G-quadruplex topology-altering ligand of L2H2-2M2EA-
6LCO
, thereby controlling thrombin activity. 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. 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.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. |
Author | Ma, Yue Ikebukuro, Kazunori Sasaki, Shogo Tera, Masayuki Nagasawa, Kazuo Hirokawa, Takatsugu |
AuthorAffiliation | Institute of Biomaterials and Bioengineering Department of Biotechnology and Life Science Tokyo University of Agriculture and Technology Tokyo Medical and Dental University Faculty of Medicine University of Tsukuba Transborder Medical Research Center Research Core Center Division of Biomedical Science |
AuthorAffiliation_xml | – sequence: 0 name: Tokyo Medical and Dental University – sequence: 0 name: Faculty of Medicine – sequence: 0 name: Transborder Medical Research Center – sequence: 0 name: Department of Biotechnology and Life Science – sequence: 0 name: University of Tsukuba – sequence: 0 name: Institute of Biomaterials and Bioengineering – sequence: 0 name: Research Core Center – sequence: 0 name: Division of Biomedical Science – sequence: 0 name: Tokyo University of Agriculture and Technology |
Author_xml | – sequence: 1 givenname: Shogo surname: Sasaki fullname: Sasaki, Shogo – sequence: 2 givenname: Yue surname: Ma fullname: Ma, Yue – sequence: 3 givenname: Takatsugu surname: Hirokawa fullname: Hirokawa, Takatsugu – sequence: 4 givenname: Kazunori surname: Ikebukuro fullname: Ikebukuro, Kazunori – sequence: 5 givenname: Masayuki surname: Tera fullname: Tera, Masayuki – sequence: 6 givenname: Kazuo surname: Nagasawa fullname: Nagasawa, Kazuo |
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Title | Regulation of thrombin activity by ligand-induced topological alteration in a thrombin-binding aptamer |
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