Natural isoflavones regulate the quadruplex-duplex competition in human telomeric DNA.
Effects of natural isoflavones on the structural competition of human telomeric G-quadruplex d[AG(3)(T(2)AG(3))(3)] and its related Watson-Crick duplex d[AG(3)(T(2)AG(3))(3)-(C(3)TA(2))(3)C(3)T] are investigated by using circular dichroism (CD), ESI-MS, fluorescence quenching measurement, CD stopped-flow kinetic experiment, UV spectroscopy and molecular modeling methods. It is intriguing to find out that isoflavones can stabilize the G-quadruplex structure but destabilize its corresponding Watson-Crick duplex and this discriminated interaction is intensified by molecular crowding environments. Kinetic experiments indicate that the dissociation rate of quadruplex (k(obs290 nm)) is decreased by 40.3% at the daidzin/DNA molar ratio of 1.0 in K(+), whereas in Na(+) the observed rate constant is reduced by about 12.0%. Furthermore, glycosidic daidzin significantly induces a structural transition of the polymorphic G-quadruplex into the antiparallel conformation in K(+). This is the first report on the recognition of isoflavones with conformational polymorphism of G-quadruplex, which suggests that natural isoflavone constituents potentially exhibit distinct regulation on the structural competition of quadruplex versus duplex in human telomeric DNA.
Zhang
Jin-li
JL
Key Laboratory of Systems Bioengineering, Ministry of Education, School of Chemical Engineering & Technology, Tianjin University, Tianjin 300072, China.
Fu
Yan
Y
Zheng
Lin
L
Li
Wei
W
Li
Hao
H
Sun
Qian
Q
Xiao
Ying
Y
Geng
Feng
F
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D007529:Isoflavones / Q000737:chemistry*; D007700:Kinetics; D009691:Nucleic Acid Denaturation; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization; D016615:Telomere / Q000737:chemistry*
D007529:Isoflavones; D004247:DNA