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Forschungsstelle
COST
Projektnummer
C97.0026
Projekttitel
Chemical Properties of Platinum and Other Metal Ion Complexes with Nucleobases and Antiviral Nucleotide Analogues (MICNANA)
Projekttitel Englisch
Chemical Properties of Platinum and Other Metal Ion Complexes with Nucleobases and Antiviral Nucleotide Analogues (MICNANA)

Texte zu diesem Projekt

 DeutschFranzösischItalienischEnglisch
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Abstract
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Erfasste Texte


KategorieText
Schlüsselwörter
(Englisch)
Antivirals; Cisplatin; Metal Ion Complexes; Nucleic Acid Polymerases; Nucleotide Analogues; Thiophosphates
Forschungsprogramme
(Englisch)
COST-Action D8 - La chimie des métaux en médecine
Kurzbeschreibung
(Englisch)
See abstract
Partner und Internationale Organisationen
(Englisch)
A, B, CZ, DK, FIN, F, D, GR, H, IRL, I, NL, N, PL, P, RO, SI, E, S, CH, GB
Abstract
(Englisch)
Among the results obtained during the period of this report (01.04.2000-30.04.2001) the following ones may be emphasized: (i) In the ternary complexes (diethylenetriamine)Pt(PMEA-N1) and (diethylenetriamine)Pt(PMEA-N7) the (Dien)Pt2+ unit is coordinated either via N1 or via N7 to the adenine residue of the dianionic nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA2-); both ternary complexes are able to bind further metal ions like Mg2+, Ca2+ or Zn2+ at the phosphonate group of PMEA2- to give M[(Dien)Pt(PMEA-N1/N7)]2+ species despite the positively charged (Dien)Pt2+ at the nucleobase. This observation is meaningful regarding the properties of the antitumor drug Cisplatin, cis-(NH3)2PtCl2, which is believed to exert its biological action by binding of cis-(NH3)2Pt2+ to the N7 sites of the purine residues in DNA, because it shows that a phosph(on)ate site of a nucleotide unit may still bind metal ions, the decrease in stability being small. (ii) By studying the extent of intramolecular stack formation in the mixed ligand complexes Cu(Arm)(PA), where Arm = 2,2'-bipyridine or 1,10-phenanthroline and PA2- = PMEA2-, 3'-deoxa-PMEA2- or adenosine 5'-monophosphate (AMP2-), it is shown that the stacking properties of AMP2- and its analogues are quite alike; this similarity contrasts with previous results obtained for binary complexes in which the properties of the antivirally acitve PMEA2- differ significantly from those of 3'-deoxa-PMEA2- or AMP2-. (iii) Studies with Pb2+ revealed that its affinity towards the various constituents of single-stranded nucleic acids decreases in the following series: guanine-N7(O6) >Ž~ cytosine-N3(O2) >Ž~ R'OP(O)-/2OR (phosphate-diester bridge) >Ž~ adenine > uracil ~ thymine. This observation is of relevance for leadzymes, i.e. for ribozymes which require Pb2+ for catalytic activity, but also for other metal ions like Zn2+ because for these the same stability order is expected. Furthermore, it was shown that the replacement of an O by an S atom in a phosphate group enhances the affinity of this group for Pb2+ and Zn2+, but not for Mg2+; these results are of relevance for corresponding thiooligonucleotides which are of potential interest in antisense therapy.
Datenbankreferenzen
(Englisch)
Swiss Database: COST-DB of the State Secretariat for Education and Research Hallwylstrasse 4 CH-3003 Berne, Switzerland Tel. +41 31 322 74 82 Swiss Project-Number: C97.0026