Bi. Kankia et La. Marky, Folding of the thrombin aptamer into a G-quadruplex with Sr2+: Stability, heat, and hydration, J AM CHEM S, 123(44), 2001, pp. 10799-10804
It has been shown that the DNA aptamer d(G(2)T(2)G(2)TGTG(2)T(2)G(2)) adopt
s an intraniolecular G-quadruplex structure in the presence of K+. Its affi
nity for trombin has been associated with the inhibition of thrombin-cataly
zed fibrin clot fort-nation. In this work, we used a combination of spectro
scopy, calorimetry, density, and ultrasound techniques to determine the spe
ctral characteristics, thermodynamics, and hydration effects for the format
ion of G-quadruplexes with a variety of monovalent and divalent metal ions.
The formation of cation-aptamer complexes is relatively fast and highly re
producible. The comparison of their CD spectra and melting profiles as a fu
nction of strand concentration shows that K+, Rb+, NH4+, Sr2+, and Ba2+-for
m intramolecular cation-aptanter complexes with transition temperatures abo
ve 25 degreesC. However, the cations Li+, Na+, Cs+, Mg2+, and Ca2+ form wea
ker complexes at very low temperatures. This is consistent with the observa
tion that metal ions with ionic radii in the range 1.3-1.5 Angstrom fit wel
l within ' the two G-quartets of the complex, while the other cations canno
t. The comparison of thermodynamic unfolding profiles of the Sr(2+)aptamer
and K+-aptamer complexes shows that the Sr2+-aptamer complex is more stable
, by similar to 18 degreesC, and unfolds with a lower endothermic heat of 8
.3 kcal/mol. This is in excellent agreement with the exothermic heats of -1
6.8 kcal/mol and -25.7 kcal/mol for the binding of Sr2+ and K+ to the aptam
er, respectively. Furthermore, volume and compressibility parameters of cat
ion binding show hydration effects resulting mainly from two contributions:
the dehydration of both cation and guanine atomic groups and water uptake
upon the folding of a single-strand into a G- quadruplex structure.