@article{discovery10096361, month = {July}, year = {2017}, number = {30}, pages = {8761--8765}, title = {Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation}, publisher = {WILEY-V C H VERLAG GMBH}, volume = {56}, note = {This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.}, journal = {Angewandte Chemie International Edition}, issn = {1521-3773}, keywords = {DNA deformation, induced-fit recognition, neurological disease, trinucleotide repeats, X-ray crystallography}, abstract = {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.}, author = {Tseng, W-H and Chang, C-K and Wu, P-C and Hu, N-J and Lee, G-H and Tzeng, C-C and Neidle, S and Hou, M-H}, url = {https://doi.org/10.1002/anie.201703989} }