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Nucleic Acids Research, 2003, Vol. 31, No. 6 1605-1613
© 2003 Oxford University Press

Platinum cross-linking of adenines and guanines on the quadruplex structures of the AG3(T2AG3)3 and (T2AG3)4 human telomere sequences in Na+ and K+ solutions

Sophie Redon1, Sophie Bombard1, Miguel-Angel Elizondo-Riojas1,2 and Jean-Claude Chottard1

1 Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR8601, Université René Descartes, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France and 2 Centro Universitario Contra el Cáncer, Hospital Universitario ‘Dr José Eleuterio González’, Universidad Autónoma de Nuevo León, Monterrey, N. L., México

*To whom correspondence should be addressed. Tel: +33 1 42 86 22 56; Fax: +33 1 42 86 83 87; Email: bombard{at}biomedicale.univ-paris5.fr

The quadruplex structures of the human telomere sequences AG3(T2AG3)3 I and (T2AG3)4 II were investigated in the presence of Na+ and K+ ions, through the cross-linking of adenines and guanines by the cis- and trans-[Pt(NH3)2(H2O)2](NO3)2 complexes 1 and 2. The bases involved in chelation of the cis- and trans-Pt(NH3)2 moieties were identified by chemical and 3'-exonuclease digestions of the products isolated after denaturing gel electrophoresis. These are the four adenines of each sequence and four out of the 12 guanines. Two largely different structures have been reported for I: A from NMR data in Na+ solution and B from X-ray data of a K+-containing crystal. Structure A alone agrees with our conclusions about the formation of the A1–G10, A13–G22, A1–A13 platinum chelates at the top of the quadruplex and A7–A19, G4–A19 and A7–G20 at the bottom, whether the Na+ or K+ ion is present. At variance with a recent proposal that structures A and B could be the major species in Na+ and K+ solutions, respectively, our results suggest that structure A exists predominantly in the presence of both ions. They also suggest that covalent platinum cross-linking of a human telomere sequence could be used to inhibit telomerase.


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