The Pressure Dependence of the Stability of the G-quadruplex Formed by d(TGGGGT)

Abstract

The G-quadruplex (GQ), a tetrahelix formed by guanine-rich nucleic acid sequences, is a potential drug target for several diseases. Monomolecular GQs are stabilized by guanine tetrads and non-guanine regions that form loops. Hydrostatic pressure destabilizes the folded, monomolecular GQ structures. In this communication, we present data on the effect of pressure on the conformational stability of the tetramolecular GQ, d[5′-TGGGGT-3′]4. This molecule does not have loops linking the tetrads; thus, its physical properties presumably reflect those of the tetrads alone. Understanding the properties of the tetrads will aid in understanding the contribution of the other structural components to the stability of GQ DNA. By measuring UV light absorption, we have studied the effect of hydrostatic pressure on the thermal stability of the tetramolecular d[5′-TGGGGT-3′]4 in the presence of sodium ions. Our data show that, unlike monomolecular GQ, the temperature at which d[5′-TGGGGT-3′]4 dissociates to form the constituent monomers is nearly independent of pressure up to 200 MPa. This implies that there is no net molar volume difference (∆V) between the GQ and the unfolded random-coil states. This finding further suggests that the large negative ∆V values for the unfolding of monomolecular GQ are due to the presence of the loop regions in those structures.

Pressure Tuning Studies of Four-Stranded Nucleic Acid Structures

“…The role of the loops in the volumetric properties of GQs was further emphasized by a recent study [ 65 ]. These authors compared the pressure effect on the stabilities of the tetramolecular d[TGGGGT] 4 GQ and the monomolecular Pu12T13T GQ.…”

“…The pressure behavior of several GQ structures has been investigated [ 14 , 26 , 46 , 51 , 61 , 62 , 63 , 64 , 65 , 66 ]. The studied sequences are listed in Table 1 , while the main results are summarized in Table 2 .…”

“…Both structures had parallel strand orientation, although TG4T GQ was stabilized by high concentrations of Na + , while PuT12T13 was formed in the presence of low concentrations of the K + ion. Since tetramolecular GQ does not have any loops, the authors concluded that the Δ V values for the monomolecular GQs are due to the presence of the loop regions in those structures [ 65 ].…”