"Head-to-head" double-hamburger-like structure of di-ruthenated d(GpG) adducts of monofunctional Ru-arene anticancer complexes

0471979 - BFÚ 2017 RIV GB eng J - Článek v odborném periodiku
Liu, H. - Kostrhunová, Hana - Habtemariam, A. - Kong, Y.Q. - Deeth, R.J. - Brabec, Viktor - Sadler, Peter J.
"Head-to-head" double-hamburger-like structure of di-ruthenated d(GpG) adducts of monofunctional Ru-arene anticancer complexes.
Dalton Transactions. Roč. 45, č. 46 (2016), s. 18676-18688. ISSN 1477-9226. E-ISSN 1477-9234
Grant CEP: GA ČR(CZ) GA14-21053S
Institucionální podpora: RVO:68081707
Klíčová slova: interstrand cross-links * nucleotide excision-repair * cis-diamminedichloroplatinum(ii) induced distortion
Kód oboru RIV: BO - Biofyzika
Impakt faktor: 4.029, rok: 2016

Guanine bases in DNA are targets for some Ru-arene anticancer complexes. We have investigated the structure of the novel di-ruthenated d(GpG) adduct Ru-2-GpG (where Ru = {(eta(2)-biphenyl)-Ru(en)}(2+) (1')) in aqueous solution. 2D NMR results indicate that there are two conformers, supported by modeling studies. The major conformer I is a novel double-hamburger-like structure with a "head-to-head" (HH) base arrangement involving hydrophobic interactions between neighboring arene rings, the first example of a HH d(GpG) adduct constructed by weak interactions. Hence there are significant differences compared to Pt-d(GpG) adducts formed by cisplatin. There is no obviously rigid bending for the major conformer I. The minor conformer II of Ru2-GpG has a back-to-back structure, with two ruthenated guanine bases flipped away from each other. 19-23 base-pair oligodeoxyribonucleotides containing central TGGT sequences di-ruthenated by 1 show no directional bending, only slightly distorted di-ruthenated duplexes, consistent with the NMR data for conformer I. The structural differences and similarities of d(GpG) residues which are di-ruthenated or cross-linked by platination are discussed in the context of the biological activity of these metal complexes.
Trvalý link: http://hdl.handle.net/11104/0269338