Stability and kinetics of G-quadruplex structures

Abstract

In this review, we give an overview of recent literature on the structure and stability of unimolecular G-rich quadruplex structures that are relevant to drug design and for in vivo function. The unifying theme in this review is energetics. The thermodynamic stability of quadruplexes has not been studied in the same detail as DNA and RNA duplexes, and there are important differences in the balance of forces between these classes of folded oligonucleotides. We provide an overview of the principles of stability and where available the experimental data that report on these principles. Significant gaps in the literature have been identified, that should be filled by a systematic study of well-defined quadruplexes not only to provide the basic understanding of stability both for design purposes, but also as it relates to in vivo occurrence of quadruplexes. Techniques that are commonly applied to the determination of the structure, stability and folding are discussed in terms of information content and limitations. Quadruplex structures fold and unfold comparatively slowly, and DNA unwinding events associated with transcription and replication may be operating far from equilibrium. The kinetics of formation and resolution of quadruplexes, and methodologies are discussed in the context of stability and their possible biological occurrence.

Specific and Sensitive Fluorescence Anisotropy Sensing of Guanine-Quadruplex Structures via a Photoinduced Electron Transfer Mechanism

“…The increased characteristic CD signal indicates more G-quadruplex formed or the enhanced stability of G-quadruplex structure. 17,42 Interestingly, the reduction in FA is inversely proportional to the increase in CD signal at 293 nm ( Figure 1D). The good correlation between FA reduction and CD signal increase in characteristic peak (R 2 = 0.987) supports the correlation of the large reduction in FA with the formation of G-quadruplex structure.…”

Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres

“…Although SWNTs do not stabilize G-quadruplex DNA, they can cause human telomeric duplex to disassociate. SWNTs-induced duplex dissociation and i-motif formation will indirectly facilitate the complementary telomeric G-rich strand [13][14][15][16] to fold into G-quadruplex structure, especially under near-physiological conditions of pH and salt concentration 19 (Fig. 1b).…”

The Human Telomere Sequence, (TTAGGG)4, in the Absence and Presence of Cosolutes: A Spectroscopic Investigation

“…DNA sequences that have islands of G 2-4 separated by 1 to 4 A and/or T bases can form a rich library of secondary structures with different molecularities, strand orientations, and guanine base conformation (i.e., syn or anti) [3][4][5][6][7][8][9][10][11][12][13][14]. The conformations and their stabilities are highly dependent upon the sequence context and buffer conditions [15][16][17][18][19][20][21].…”

“…A model was presented for the quadruplex to random coil transition, via formation of an unknown intramolecular intermediate, with exclusion of K + during each transition. Review of the literature reveals that different investigators have used slight variations of the sequence (TTAGGG) 4 for their investigations and have drawn conclusions based upon their data [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. We recently reported however that changing just one base in just one loop of the folded quadruplex influences both conformation and stability [20].…”