Natural isoflavones regulate the quadruplex-duplex competition in human telomeric DNA

Abstract

Effects of natural isoflavones on the structural competition of human telomeric G-quadruplex d[AG3(T2AG3) 3] and its related Watson-Crick duplex d[AG3 (T2AG3)3-(C3TA2) 3C3T] 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 (kobs290 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.