Document Detail

Interaction of Polycationic Ni(II)-Salophen Complexes with G-Quadruplex DNA.
MedLine Citation:
PMID:  25383703     Owner:  NLM     Status:  Publisher    
A series of nine Ni(II) salophen complexes involving one, two, or three alkyl-imidazolium side-chains was prepared. The lengths of the side-chains were varied from one to three carbons. The crystal structure of one complex revealed a square planar geometry of the nickel ion. Fluorescence resonance energy transfer melting of G-quadruplex structures in the presence of salophen complex were performed. The G-quadruplex DNA structures were stabilized in the presence of the complexes, but a duplex DNA was not. The binding constants of the complexes for parallel and antiparallel G-quadruplex DNA, as well as hairpin DNA, were measured by surface plasmon resonance. The compounds were selective for G-quadruplex DNA, as reflected by equilibrium dissociation constant KD values in the region 0.1-1 μM for G-quadruplexes and greater than 2 μM for duplex DNA. Complexes with more and shorter side-chains had the highest binding constants. The structural basis for the interaction of the complexes with the human telomeric G-quadruplex DNA was investigated by computational studies: the aromatic core of the complex stacked over the last tetrad of the G-quadruplex with peripherical cationic side chains inserted into opposite grooves. Biochemical studies (telomeric repeat amplification protocol assays) indicated that the complexes significantly inhibited telomerase activity with IC50 values as low as 700 nM; the complexes did not significantly inhibit polymerase activity.
Laureline Lecarme; Enora Prado; Aurore De Rache; Marie-Laure Nicolau-Travers; Romaric Bonnet; Angeline van Der Heyden; Christian Philouze; Dennis Gomez; Jean-Louis Mergny; Hélène Jamet; Eric Defrancq; Olivier Jarjayes; Fabrice Thomas
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-11-10
Journal Detail:
Title:  Inorganic chemistry     Volume:  -     ISSN:  1520-510X     ISO Abbreviation:  Inorg Chem     Publication Date:  2014 Nov 
Date Detail:
Created Date:  2014-11-10     Completed Date:  -     Revised Date:  2014-11-11    
Medline Journal Info:
Nlm Unique ID:  0366543     Medline TA:  Inorg Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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