Journal
JOURNAL OF MOLECULAR STRUCTURE
Volume 1141, Issue -, Pages 357-367Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molstruc.2017.03.115
Keywords
H-1 NMR; DNA; Anticancer drug; C-1311; Symadex; Intercalation
Categories
Ask authors/readers for more resources
Imidazoacridinone C-1311 (Symadex (R)) is an antitumor agent which has been recommended for Phase II clinical trials a few years ago. Previously, it was shown experimentally that during the initial stage of its action C-1311 forms stable intercalation complexes with DNA duplexes. Herein, a NMR-derived stereo structure of d(GAGGCCTC)(2):C-1311 complex was reported. The ligand was found locating itself between A and G moieties, forming symmetrical DNA:drug 1:2 mol/mol complex. Intercalation site was located upon the DNA-ligand proton/proton dipolar couplings observed in the NOESY spectrum and the performed MD simulations. NMR-derived stereostructure was hence refined by restrained MD using distance restraints obtained from the NOESY data and the result was compared with MD-derived structure of the proposed complex, obtained from the calculations performed with distance restraints applied only for hydrogen bonds in the terminal GC base pairs. The results of both simulations were coherent. Basing on the observed C-1311's intercalation sites and on our previous results concerning the d(CGATCG)(2):C-1311 complex, we stated that AG/GA sequences are the preferred binding sites of imidazoacridinone C-1311. (C) 2017 Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available