TY - JOUR
T1 - Hydration is a major determinant of the G-quadruplex stability and conformation of the human telomere 3′ sequence of d(AG 3(TTAG3)3)
AU - Miller, M. Clarke
AU - Buscaglia, Robert
AU - Chaires, Jonathan B.
AU - Lane, Andrew N.
AU - Trent, John O.
PY - 2010/12/8
Y1 - 2010/12/8
N2 - The factors that determine the conformation and stability of G-quadruplex forming sequences remain poorly understood. Here we demonstrate the influence of cosolvents on the conformation and stability of the human telomeric sequence d(A(GGGTTA)3GGG)) in both K+ and Na+ containing solutions using a combination of circular dichroism, NMR, and thermodynamics. Molecular crowding arguments have previously been used to suggest that the parallel quadruplex form may be biologically relevant. However, the small cosolvents previously used, PEG 200 and 400, are actually dehydrating agents. We have used acetonitrile as a non-hydrogen-bonding dehydrating agent; similar conformational transitions were observed in K+ solution. Moreover, NMR analysis shows that the resulting structure contains non-anti guanine glycosyl torsion angles suggesting that the conformation present in acetonitrile is not identical to the all-parallel crystal structure, despite the supposed parallel type CD spectrum.
AB - The factors that determine the conformation and stability of G-quadruplex forming sequences remain poorly understood. Here we demonstrate the influence of cosolvents on the conformation and stability of the human telomeric sequence d(A(GGGTTA)3GGG)) in both K+ and Na+ containing solutions using a combination of circular dichroism, NMR, and thermodynamics. Molecular crowding arguments have previously been used to suggest that the parallel quadruplex form may be biologically relevant. However, the small cosolvents previously used, PEG 200 and 400, are actually dehydrating agents. We have used acetonitrile as a non-hydrogen-bonding dehydrating agent; similar conformational transitions were observed in K+ solution. Moreover, NMR analysis shows that the resulting structure contains non-anti guanine glycosyl torsion angles suggesting that the conformation present in acetonitrile is not identical to the all-parallel crystal structure, despite the supposed parallel type CD spectrum.
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U2 - 10.1021/ja105259m
DO - 10.1021/ja105259m
M3 - Article
C2 - 21087016
AN - SCOPUS:78650109518
SN - 0002-7863
VL - 132
SP - 17105
EP - 17107
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 48
ER -