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"Mechanical Properties of DNA G-Quadruplex Structures"

The conformation of G-quadruplex is an important property for applications based on this structure. For example, Miyoshi reported the formation of G-wire, a high-order nanostructure assembled by parallel G-quadruplex units.¹ The conformation-specific catalytic activity of G-quadruplex structures has been demonstrated. The thrombin binding aptamer, known to assume an antiparallel structure in K⁺ buffer, catalyses an aldol reaction between a ketone and a porphyrin-linked aldehyde.² G-quadruplex structures with millimolar DNA concentrations are determined by ensemble techniques such as NMR and X-ray crystallography. At such high concentrations, a mixture of conformations exists which is difficult to resolve for these methods. Single-molecule methods are ideal tools to profile conformations under these conditions.

Force based single-molecule methods can reach Angstrom (Å) resolution of individual species, and therefore are suitable for detailed characterization of structures in a solution mixture. In addition, force-based approaches can reveal mechanical stability of a structure and provide thermodynamic information such as change in the free energy of unfolding (∆G_unfold) of the structure. For many materials-related applications that employ G-quadruplexes as essential building blocks, mechanical stability is a rather important indicator to reflect the robustness of a device under strained environment. Therefore, revealing the mechanical stability of G-quadruplex nanostructures can provide useful insights to design nanomaterial devices for applications in nanotech and biotech fields. In our projects, we will use home-built optical tweezers instrument to illustrate G-quadruplex nanostructures formed in various sequences such as telomeres and gene promoter regions. We will identify specific G-quadruplex conformations in these sequences first and then examine the mechanical properties of these structures for their applications in nanodevices.

1. D. Miyoshi, A. Nakao, and N. Sugimoto, Structural transition from antiparallel to parallel G-quadruplex of d(G4T4G4) induced by Ca2+, Nucleic Acids Research 31, 1156-1163 (2003).
2. Z. Tang, D.P.N. Gonçalves, M. Wieland, A. Marx, and J. S. Hartig, Novel DNA catalysts based on G-quadruplex recognition, Chem.Bio.Chem. 9, 1061-1064 (2008).