Dynamic insight into the interaction between porphyrin and G-quadruplex DNAs: time-resolved fluorescence anisotropy study.
Understanding the nature of the interaction between small molecules and G-quadruplex DNA is crucial for the development of novel anticancer drugs. In this paper, we present the first data on time-resolved fluorescence anisotropy study on the interaction between a water-soluble cationic porphyrin H(2)TMPyP4 and four distinct G-quadruplex DNAs, that is, AG(3)(T(2)AG(3))(3), thrombin-binding aptamer (TBA), (G(4)T(4)G(4))2, and (TG(4)T)4. The anisotropy decay curves show the monoexponential for free H(2)TMPyP4 and the biexponential upon binding to the excess amount of G-quadruplex DNAs. The biexponential anisotropy decay can be well interpreted using a wobbling-in-the-cone model. The orientational diffusion of the bound H(2)TMPyP4 is initially restricted to a limited cone angle within the G-quadruplex DNAs, and then an overall orientational relaxation of the G-quadruplex DNA-H(2)TMPyP4 complexes occurs in a longer time scale. It was found that the dynamics of the restricted internal rotation of bound H(2)TMPyP4 strongly depends on the ending structures of the G-quadruplex DNAs. According to the order parameter (Q) calculated from the wobbling-in-the-cone model, we deduce that the degree of restriction around the bound H(2)TMPyP4 follows the order of TBA > (TG(4)T)4 > AG(3)(T(2)AG(3))(3) > (G(4)T(4)G(4))2. Especially, based on the maximum order parameter (Q) of bound H(2)TMPyP4 within TBA, a new sandwich-type binding mode for TBA-H(2)TMPyP4 complex was proposed in which both terminal G-quartet and T*T base pair stack on the porphyrin ring through pi-pi interaction. This study thus provides a new insight into the interaction between G-quadruplex DNAs and H(2)TMPyP4.
Jia
Guoqing
G
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Feng
Zhaochi
Z
Wei
Chunying
C
Zhou
Jun
J
Wang
Xiuli
X
Li
Can
C
D052157:Aptamers, Nucleotide / Q000737:chemistry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D005454:Fluorescence Polarization; D054856:G-Quadruplexes; D056004:Molecular Dynamics Simulation; D011166:Porphyrins / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D052157:Aptamers, Nucleotide; D011166:Porphyrins; C081676:thrombin aptamer; D004247:DNA