Imperial College London

Prof. Ramon Vilar

Faculty of Natural SciencesDepartment of Chemistry

Professor of Medicinal Inorganic Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 1967r.vilar Website

 
 
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Location

 

301HMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Gama:2016:10.1016/j.jinorgbio.2016.04.002,
author = {Gama, S and Rodrigues, I and Mendes, F and Santos, IC and Gabano, E and Klejevskaja, B and Gonzalez-Garcia, J and Ravera, M and Vilar, R and Paulo, A},
doi = {10.1016/j.jinorgbio.2016.04.002},
journal = {Journal of Inorganic Biochemistry},
pages = {275--286},
title = {Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders},
url = {http://dx.doi.org/10.1016/j.jinorgbio.2016.04.002},
volume = {160},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - The formation of quadruple-stranded DNA induced by planar metal complexes has particular interest in the development of novel anticancer drugs. This is especially relevant for the inhibition of telomerase, which plays an essential role in cancer cell immortalization and is overexpressed in ca. 85-90% of cancer cells. Moreover, G-quadruplexes also exist in other locations in the human genome, namely oncogene promoter regions, and it has been hypothesized that they play a regulatory role in gene transcription. Herein we report a series of new anthracene-containing terpyridine ligands and the corresponding Cu(II) and Pt(II) complexes, with different linkers between the anthracenyl moiety and the terpyridine chelating unit. The interaction of these ligands and metal complexes with different topologies of DNA was studied by several biophysical techniques. The Pt(II) and Cu(II) complexes tested showed affinity for quadruplex-forming sequences with a good selectivity over duplex DNA. Importantly, the free ligands do not have significant affinity for any of the DNA sequences used, which shows that the presence of the metal is essential for high affinity (and selectivity). This effect is more evident in the case of the Pt(II) complexes. Moreover, the presence of a longer linker between the chelating terpyridine unit and the anthracene moiety enhances the interaction with G-quadruplex-forming sequences. We further evaluated the ability of the Cu(II) complexes to interact with, and stabilize G-quadruplex containing regions in oncogene promoters via a polymerase stop assay. These studies indicated that the metal complexes are able to induce G-quadruplex formation and stop polymerase activity.
AU - Gama,S
AU - Rodrigues,I
AU - Mendes,F
AU - Santos,IC
AU - Gabano,E
AU - Klejevskaja,B
AU - Gonzalez-Garcia,J
AU - Ravera,M
AU - Vilar,R
AU - Paulo,A
DO - 10.1016/j.jinorgbio.2016.04.002
EP - 286
PY - 2016///
SN - 1873-3344
SP - 275
TI - Anthracene-terpyridine metal complexes as new G-quadruplex DNA binders
T2 - Journal of Inorganic Biochemistry
UR - http://dx.doi.org/10.1016/j.jinorgbio.2016.04.002
VL - 160
ER -