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

By Jin-li Zhang, Yan Fu, Lin Zheng, Wei Li, Hao Li, Qian Sun, Ying Xiao and Feng Geng

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

Topics: Structural Biology
Publisher: Oxford University Press
OAI identifier: oai:pubmedcentral.nih.gov:2677859
Provided by: PubMed Central

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