%0 Journal Article
%@ 1521-3773
%A Tseng, W-H
%A Chang, C-K
%A Wu, P-C
%A Hu, N-J
%A Lee, G-H
%A Tzeng, C-C
%A Neidle, S
%A Hou, M-H
%D 2017
%F discovery:10096361
%I WILEY-V C H VERLAG GMBH
%J Angewandte Chemie International Edition
%K DNA deformation, induced-fit recognition, neurological disease, trinucleotide repeats, X-ray crystallography
%N 30
%P 8761-8765
%T Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation
%U https://discovery.ucl.ac.uk/id/eprint/10096361/
%V 56
%X Small‐molecule compounds targeting trinucleotide repeats in DNA have considerable potential as therapeutic or diagnostic agents against many neurological diseases. Ni^{II}(Chro)_{2} (Chro=chromomycin A3) binds specifically to the minor groove of (CCG)_{n} repeats in duplex DNA, with unique fluorescence features that may serve as a probe for disease detection. Crystallographic studies revealed that the specificity originates from the large‐scale spatial rearrangement of the DNA structure, including extrusion of consecutive bases and backbone distortions, with a sharp bending of the duplex accompanied by conformational changes in the Ni^{II} chelate itself. The DNA deformation of CCG repeats upon binding forms a GGCC tetranucleotide tract, which is recognized by Ni^{II}(Chro)_{2}. The extruded cytosine and last guanine nucleotides form water‐mediated hydrogen bonds, which aid in ligand recognition. The recognition can be accounted for by the classic induced‐fit paradigm.
%Z This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.