title: Porphyrin derivatives for telomere binding and telomerase inhibition.
abstract: The 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.
authors.affiliation: Laboratoire de Chimie de Coordination, CNRS UPR 8241, 205 route de Narbonne, 31077 Toulouse Cedex 4, France.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Dixon
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lopez
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Estève
authors.forename: Agueda M
authors.initials: AM
authors.lastname: Tejera
authors.forename: María A
authors.initials: MA
authors.lastname: Blasco
authors.forename: Geneviève
authors.initials: G
authors.lastname: Pratviel
authors.forename: Bernard
authors.initials: B
authors.lastname: Meunier
mesh_terms: D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D054856:G-Quadruplexes; D006801:Humans; D008345:Manganese / Q000737:chemistry / Q000378:metabolism; D008665:Metalloporphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009532:Nickel / Q000737:chemistry / Q000378:metabolism; D021141:Nucleic Acid Amplification Techniques; D020349:Surface Plasmon Resonance; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D008345:Manganese; D009532:Nickel; D004247:DNA; D019098:Telomerase