Binding of a Telomestatin Derivative Changes Mechanical Anisotropy of Human Telomeric G‐Quadruplex

Sagun Jonchhe, Chiran Ghimire, Yunxi Cui, Shogo Sasaki, Mason McCool, Soyoung Park, Keisuke Iida, Prof. Kazuo Nagasawa, Prof. Hiroshi Sugiyama, Prof. Hanbin Mao

Mechanical anisotropy is an essential property for biomolecules to assume structural and functional roles in mechanobiology. However, there is insufficient information on the mechanical anisotropy of ligand–biomolecule complexes. Herein, we investigated the mechanical property of individual human telomeric G‐quadruplexes bound to telomestatin, using optical tweezers. Stacking of the ligand to the G‐tetrad planes changes the conformation of the G‐quadruplex, which resembles a balloon squeezed in certain directions. Such a squeezed balloon effect strengthens the G‐tetrad planes, but dislocates and weakens the loops in the G‐quadruplex upon ligand binding. These dynamic interactions indicate that the binding between the ligand and G‐quadruplex follows the induced‐fit model. We anticipate that the altered mechanical anisotropy of the ligand–G‐quadruplex complex can add additional level of regulations on the motor enzymes that process DNA or RNA molecules.

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