Porphyrin Derivatives for Telomere Binding and Telomerase Inhibition

ChemBioChem - Tập 6 Số 1 - Trang 123-132 - 2005
Isabelle M. Dixon1, Frédéric Lopez2, Jean‐Pierre Estève3, Águeda M. Tejera4, Marı́a A. Blasco4, Geneviève Pratviel1, Bernard Meunier1
1Laboratoire de Chimie de Coordination, CNRS UPR 8241, 205 route de Narbonne, 31077 Toulouse Cedex 4, France, Fax: (+33) 561-553-003
2INSERM IFR 31, Institut Louis Bugnard, Hôpital Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France
3INSERM U 531, Institut Louis Bugnard, Hôpital Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France
4Spanish National Cancer Center, Melchor Fernández Almagro 3, 28029 Madrid, Spain

Tóm tắt

AbstractThe capacity of G‐quadruplex ligands to stabilize four‐stranded DNA makes them able to inhibit telomerase, which is involved in tumour cell proliferation. A series of cationic metalloporphyrin derivatives was prepared by making variations on a meso‐tetrakis(4‐N‐methyl‐pyridiniumyl)porphyrin skeleton (TMPyP). The DNA binding properties of nickel(II) and manganese(III) porphyrins were studied by surface plasmon resonance, and the capacity of the nickel porphyrins to inhibit telomerase was tested in a TRAP assay. The nature of the metal influences the kinetics (the process is faster for Ni than for Mn) and the mode of interaction (stacking or external binding). The chemical alterations did not lead to increased telomerase inhibition. The best selectivity for G‐quadruplex DNA was observed for Mn‐TMPyP, which has a tenfold preference for quadruplex over duplex.

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