1 research outputs found
Ionic Effects on VEGF G‑Quadruplex Stability
In
a potassium solution, a modified 22-meric DNA sequence Pu22-T12T13
from a region proximal to the transcription initiation site of the
human VEGF gene adopts a single parallel-stranded G-quadruplex conformation
with a 1:4:1 loop-size arrangement. We measured the thermal stability, <i>T</i><sub>M</sub>, of the K<sup>+</sup>-stabilized Pu22-T12T13
G-quadruplex as a function of stabilizing K<sup>+</sup> ions and nonstabilizing
Cs<sup>+</sup> and TMA<sup>+</sup> ions. The thermal stability, <i>T</i><sub>M</sub>, of the Pu22-T12T13 G-quadruplex increases
with the concentration of the stabilizing potassium ions, while it
sharply decreases upon the addition of the nonstabilizing cations.
We interpret these results as underscoring the opposing effects of
internal binding and counterion condensation on the stability of the
Pu22-T12T13 G-quadruplex. While centrally bound ions stabilize the
G-quadruplex conformation, counterion condensation destabilizes it,
favoring the coil conformation. From the initial slopes of the dependences
of <i>T</i><sub>M</sub> on the concentration of Cs<sup>+</sup> and TMA<sup>+</sup> cations, we estimate that the deleterious effect
of counterion condensation stems from roughly one extra counterion
associated with the coil relative to the G-quadruplex state of Pu22-T12T13.
The reduced accumulation of counterions around the G-quadruplex state
of Pu22-T12T13 relative to its coil state is due to the low surface
charge density of the G-quadruplex reflecting its structural characteristics.
On the basis of the analysis of our data along with the results of
a previous study, we propose that the differential effect of internally
(stabilizing) and externally (destabilizing) bound cations may be
a general feature of parallel intramolecular G-quadruplexes