Dr. Hanbin Mao
"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 (∆Gunfold) 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.
- 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).
- 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).