TY  - JOUR
PB  - WILEY-V C H VERLAG GMBH
Y1  - 2017/07/17/
A1  - Tseng, W-H
A1  - Chang, C-K
A1  - Wu, P-C
A1  - Hu, N-J
A1  - Lee, G-H
A1  - Tzeng, C-C
A1  - Neidle, S
A1  - Hou, M-H
IS  - 30
TI  - Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation
KW  - DNA deformation
KW  -  induced-fit recognition
KW  -  neurological disease
KW  -  trinucleotide repeats
KW  -  X-ray crystallography
UR  - https://doi.org/10.1002/anie.201703989
SP  - 8761
AV  - public
JF  - Angewandte Chemie International Edition
EP  - 8765
SN  - 1521-3773
N1  - This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
ID  - discovery10096361
VL  - 56
N2  - 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.
ER  -