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Metal ion-nucleic acid interactions and antitumour drugs

Objective

The research groups of the network will collaborate by approaching the complex theme of the study of the interactions between inorganic systems and nucleic acids and their related pharmacological effects, especially their antitumour activity, by different complementary methods. The different themes that will be developed are platinum-based, ruthenium-based, other transition metal-based and tin-based antitumour drugs.The results one can expect from this type of investigation are: finding of new inorganic drugs and new insights in the structure-activity relationship; a better understanding of metal nucleic acid functionality and their role within the living systems; and a better knowledge of the relevance on metals in the living matter, together with their physiological and toxicological effects.
Research groups have collaborated in the study of the interactions between inorganic systems and nucleic acids and their related pharmacological effects, especially their antitumour activity, by different complementary methods. Results are as follows:
the interaction between platinum and palladium based antitumour drugs and nucleic acids has been studied, and structural investigations of binary peptide and ternary peptide nucleobase complexes of palladium(II) as well as of mixed platinum(II)-palladium(II) and platinum(II)-mercury(II) cytosine nucleobase compounds has been carried out;
the distortions induced in deoxyribonucleic acid (DNA) by cis or trans diamminedichloroplatinum (DDP) interstrand cross links have been characterized by deoxyribonuclease (DNase) I footprinting experiments;
the structures of the photoadducts formed between the guanosine-5'-monophosphate (GMP) and several ruthenium(II) complexes of polyazaaromatic ligands like Ru(TAP)32+ have been determined; it has been shown that the adduct is formed via covalent binding of a TAP ligand to the nitrogen 2 of guanine;
a series of diethylenetriamine pentaacetic acid (DTPA) bis amides and their lanthanum(III) complexes were prepared and characterized, as potential contrast agents for magnetic resonance imaging (MRI);
the substitution of hydrogen of fluorine, increasing the solubility of organotin compounds, has been shown to increase also their in vitro antitumour properties against human tumour cell lines.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Vrije Universiteit Brussel
Address
2,Pleinlaan 2
1050 Bruxelles
Belgium

Participants (22)

Birkbeck College
United Kingdom
Address
29 Gordon Square
WC1H 0PP London
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Route De Narbonne 205
31077 Toulouse
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Charles Sadron
45071 Orleans
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Des Saints-pères 45, Université De Paris 5
75270 Paris
LEIDEN UNIVERSITY
Netherlands
Address
55,Einsteinweg 55 Gorlaeus Laboratoria
2300 RA Leiden
National Technical University of Athens
Greece
Address
9,Heroon Politechniou 9
15780 Athens
Royal College of Surgeons in Ireland
Ireland
Address
123,Saint Stephen's Green
2 Dublin
Ruprecht-Karls-Universität Heidelberg
Germany
Address
Im Neuenheimer Feld 270
69120 Heidelberg
THE PROVOST, FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN HEREINAFTER TRINITY COLLEGE DUBLIN
Ireland
Address
Belfield
4 Dublin
UNIVERSIDAD DE SEVILLA
Spain
Address
Campus De Reina Mercedes
41012 Sevilla
UNIVERSITAT DE BARCELONA
Spain
Address
Gran Via De Les Corts Catalanes 585
Barcelona
UNIVERSITAT DE VALENCIA
Spain
Address
50,Avda Doctor Moliner 50
46100 Burjasot
UNIVERSITY OF BERGEN
Norway
Address
41,Allegt. 40
5007 Bergen
UNIVERSITÀ DEGLI STUDI DI TRIESTE
Italy
Address
Via Licio Giorgieri 1
34127 Trieste
Universidad Católica de Chile
Chile
Address
4860,Avda. Vicuña Mackenna
6177 Santiago
Universidade de Coimbra
Portugal
Address
3126,Apartado 3126
3000 Coimbra
University of Ioannina
Greece
Address
1,Salamaga
45110 Ioannina
Università degli Studi di Bari
Italy
Address
Via Orabona 4
70125 Bari
Università degli Studi di Udine
Italy
Address
Gervasutta 48
33100 Udine
Universität Basel
Switzerland
Address
51,Spitalstraße
4056 Basel
Universität Dortmund
Germany
Address

44201 Dortmund
Université Libre de Bruxelles
Belgium
Address
50,Avenue F.d. Roosevelt
1050 Bruxelles