4.4 Article

Binding of the alkaloid coralyne to parallel G-quadruplex DNA [d(TTGGGGT)]4 studied by multi-spectroscopic techniques

Journal

BIOPHYSICAL CHEMISTRY
Volume 219, Issue -, Pages 49-58

Publisher

ELSEVIER
DOI: 10.1016/j.bpc.2016.09.006

Keywords

Parallel G-quadruplex DNA; Alkaloid coralyne; Circular dichroism; Absorbance and fluorescence; Nuclear magnetic resonance; Non-intercalative binding

Funding

  1. Ministry of Human Resources and Development (MHRD), Govt. of India [MHR02-23-200-429]

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Binding of coralyne to tetra-molecular parallel G-quadruplex DNA [d(TTGGGGT)](4) was evaluated for the first time using biophysical techniques. Absorbance titration show hypo/hyper-chromism accompanied by 12 nm red shift with binding constant K-b = 02-4.0 x 10(6) M-1. Binding induces a negative circular dichroism band of coralyne at 315 nm. Quenching of fluorescence (similar to 64%) along with 10 nm blue shift in emission maxima indicates proximity of coralyne to guanine bases. Job plot indicates existence of multiple complexes. The observed two fluorescence life times, 6 and 12 ns, with relative abundance 33% and 63%, respectively suggest two binding sites/conformations in complex. ID H-1 NMR spectra reveal significant broadening and upfield shift of G3NH, G6NH and G3H8 proton signals upon binding. The NOESY spectra reveal sequence specific non-intercalative interaction of coralyne in monomeric form at two sites close to A3/G3 and G6 bases of [d(TTGGGGT)](4) and [d(TTAGGGT)](4), which has implications in anti-cancer drug action. (C) 2016 Elsevier B.V. All rights reserved.

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