Induced-fit recognition of DNA by organometallic complexes with dynamic stereogenic centers

0127044 - BFU-R 20033132 RIV US eng J - Journal Article
Chen, H. - Parkinson, J. A. - Nováková, Olga - Bella, J. - Wang, F. - Dawson, A. - Gould, R. - Parsons, S. - Brabec, Viktor - Sadler, P. J.
Induced-fit recognition of DNA by organometallic complexes with dynamic stereogenic centers.
Proceedings of the National Academy of Sciences of the United States of America. Roč. 100, č. 25 (2003), s. 14623-14628. ISSN 0027-8424. E-ISSN 1091-6490
R&D Projects: GA ČR GA305/02/1552; GA ČR GA305/01/0418; GA AV ČR IAA5004101
Institutional research plan: CEZ:AV0Z5004920
Keywords : organometallic complexes * platinum * DNA
Subject RIV: BO - Biophysics
Impact factor: 10.272, year: 2003

The stereochemistry of the dinuclear complex [((eta(6)-biphenyl)RuCl(en))(2)-(CH2)(6)](2+) (3, en = ethylenediamine) was elucidated by studies of the half unit [(eta(6)-biphenyl)RuCl(Et-en)](+) (2, where Et-en is Et(H)NCH2CH2NH2). The structures of the separated R*R-Ru*(N) and S*R-Ru*(N) diastereomers of 2 were determined by x-ray crystallography. X-ray and NMR studies showed that dynamic chiral recognition of quanine can lead to high diastereoselectivity of DNA binding. The dinuclear complex induced a large unwinding of plasmid DNA and effectively inhibited DNA-directed RNA synthesis in vitro. It gave rise to interstrand cross-links on plasmid DNA, and to 1,3-GG interstrand and 1,2-GG and 1,3-GTG intrastrand cross-links on site specifically ruthenated 20-mers. The concept of induced-fit recognition of DNA by organometallic complexes containing dynamic stereogenic centers via epimerization, intercalation, and cross-linking may be useful in the design of anticancer drugs.
Permanent Link: http://hdl.handle.net/11104/0025268