title: Toward the design of a catalytic metallodrug: selective cleavage of G-quadruplex telomeric DNA by an anticancer copper-acridine-ATCUN complex.
abstract: Telomeric DNA represents a novel target for the development of anticancer drugs. By application of a catalytic metallodrug strategy, a copper-acridine-ATCUN complex (CuGGHK-Acr) has been designed that targets G-quadruplex telomeric DNA. Both fluorescence solution assays and gel sequencing demonstrate the CuGGHK-Acr catalyst to selectively bind and cleave the G-quadruplex telomere sequence. The cleavage pathway has been mapped by matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) experiments. CuGGHK-Acr promotes significant inhibition of cancer cell proliferation and shortening of telomere length. Both senescence and apoptosis are induced in the breast cancer cell line MCF7.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, OH 43210 (USA).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yu
authors.forename: Menglu
authors.initials: M
authors.lastname: Han
authors.forename: James A
authors.initials: JA
authors.lastname: Cowan
mesh_terms: D000166:Acridines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002384:Catalysis; D002417:Cattle; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000494:pharmacology*; D054856:G-Quadruplexes; D061986:MCF-7 Cells; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016615:Telomere / Q000235:genetics*
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D003300:Copper; D004247:DNA
keywords: DNA cleavage; anticancer agents; bioinorganic chemistry; carbon; peptides