Regulation of thrombin activity by ligand-induced topological alteration in a thrombin-binding aptamer.

Autor: Sasaki S; Department 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., Ma Y; Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.; Research Core Center, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan., Hirokawa T; Transborder Medical Research Center, University of Tsukuba, Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.; Division of Biomedical Science, Faculty of Medicine, University of Tsukuba, Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan., Ikebukuro K; Department 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., Tera M; Department 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., Nagasawa K; Department 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.
Jazyk: angličtina
Zdroj: Chemical communications (Cambridge, England) [Chem Commun (Camb)] 2023 Jul 13; Vol. 59 (57), pp. 8862-8865. Date of Electronic Publication: 2023 Jul 13.
DOI: 10.1039/d3cc02308g
Abstrakt: 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.
Databáze: MEDLINE
Externí odkaz: