期刊
BIOCHIMIE
卷 93, 期 8, 页码 1318-1327出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2011.05.017
关键词
G-quadruplex DNA; Quadruplex-ligand interaction; Molecular crowding conditions; Isothermal titration calorimetry; Molecular modeling; Circular dichroism
资金
- Associazione Italiana per la Ricerca sul Cancro (A.I.R.C.) [6255]
- Italian Institute of Technology (IIT)
- COST Action [MP0802]
- Cancer Research UK
The present study has employed a combination of spectroscopic, calorimetric and computational methods to explore the binding of the three side-chained triazatruxene derivative, termed azatrux, to a human telomeric G-quadruplex sequence, under conditions of molecular crowding. The binding of azatrux to the tetramolecular parallel [d(TGGGGT)](4) quadruplex in the presence and absence of crowding conditions, was also characterized. The data indicate that azatrux binds in an end-stacking mode to the parallel G-quadruplex scaffold and highlights the key structural elements involved in the binding. The selectivity of azatrux for the human telomeric G-quadruplex relative to another biologically relevant G-quadruplex (c-Kit87up) and to duplex DNA was also investigated under molecular crowding conditions, showing that azatrux has good selectivity for the human telomeric G-quadruplex over the other investigated DNA structures. (C) 2011 Elsevier Masson SAS. All rights reserved.
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