6 research outputs found
Folding Thermodynamics of the Hybrid-1 Type Intramolecular Human Telomeric GQuadruplex
Guanine-rich DNA sequences that may form
G-quadruplexes are located in strategic DNA loci with
the ability to regulate biological events. G-quadruplexes
have been under intensive scrutiny owing to their potential
to serve as novel drug targets in emerging anticancer
strategies. Thermodynamic characterization of
G-quadruplexes is an important and necessary step in
developing predictive algorithms for evaluating the conformational
preferences of G-rich sequences in the presence
or the absence of their complementary C-rich
strands. We use a combination of spectroscopic, calorimetric,
and volumetric techniques to characterize the
folding/unfolding transitions of the 26-meric human telomeric
sequence d[A3G3(T2AG3)3A2]. In the presence of
K1 ions, the latter adopts the hybrid-1 G-quadruplex
conformation, a tightly packed structure with an unusually
small number of solvent-exposed atomic groups. The
K1-induced folding of the G-quadruplex at room temperature
is a slow process that involves significant accumulation
of an intermediate at the early stages of the
transition. The G-quadruplex state of the oligomeric
sequence is characterized by a larger volume and compressibility
and a smaller expansibility than the coil state.
These results are in qualitative agreement with each other
all suggesting significant dehydration to accompany the
G-quadruplex formation. Based on our volume data,
432619 water molecules become released to the bulk
upon the G-quadruplex formation. This large number is
consistent with a picture in which DNA dehydration is
not limited to water molecules in direct contact with the
regions that become buried but involves a general
decrease in solute–solvent interactions all over the surface
of the folded structure. VC 2013 Wiley Periodicals, Inc.
Biopolymers 101: 216–227, 2014.
Keywords: G-quadruplexes; conformational transitions;
volume; compressibility; expansibilit