eprintid: 10096361
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/09/63/61
datestamp: 2020-04-27 13:57:55
lastmod: 2021-10-03 23:47:43
status_changed: 2020-04-27 13:57:55
type: article
metadata_visibility: show
creators_name: Tseng, W-H
creators_name: Chang, C-K
creators_name: Wu, P-C
creators_name: Hu, N-J
creators_name: Lee, G-H
creators_name: Tzeng, C-C
creators_name: Neidle, S
creators_name: Hou, M-H
title: Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D10
keywords: DNA deformation, induced-fit recognition, neurological disease, trinucleotide repeats, X-ray crystallography
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions.
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.
date: 2017-07-17
date_type: published
publisher: WILEY-V C H VERLAG GMBH
official_url: https://doi.org/10.1002/anie.201703989
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1297271
doi: 10.1002/anie.201703989
lyricists_name: Neidle, Stephen
lyricists_id: SNEID18
actors_name: Kalinowski, Damian
actors_id: DKALI47
actors_role: owner
full_text_status: public
publication: Angewandte Chemie International Edition
volume: 56
number: 30
pagerange: 8761-8765
pages: 5
issn: 1521-3773
citation:        Tseng, W-H;    Chang, C-K;    Wu, P-C;    Hu, N-J;    Lee, G-H;    Tzeng, C-C;    Neidle, S;           Tseng, W-H;  Chang, C-K;  Wu, P-C;  Hu, N-J;  Lee, G-H;  Tzeng, C-C;  Neidle, S;  Hou, M-H;   - view fewer <#>    (2017)    Induced-Fit Recognition of CCG Trinucleotide Repeats by a Nickel-Chromomycin Complex Resulting in Large-Scale DNA Deformation.                   Angewandte Chemie International Edition , 56  (30)   pp. 8761-8765.    10.1002/anie.201703989 <https://doi.org/10.1002/anie.201703989>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10096361/1/Neidle_Induced-Fit%20Recognition%20of%20CCG%20Trinucleotide%20Repeats%20by%20a%20Nickel-Chromomycin%20Complex%20Resulting%20in%20Large-Scale%20DNA%20Deformation_AAM.pdf