title: Taxol anticancer activity and DNA binding.
abstract: The interaction of taxol with DNA has major biological importance since it is shown the presence of higher concentration of taxol in the nucleus, than in the human lung tumor cell. Therefore, in this report we examine the interaction of taxol with calf-thymus DNA in aqueous solution at physiological pH, using constant DNA concentration (25 or 1.25 mM phosphate) and various taxol/DNA (phosphate) ratios 1/200 to 1/2. Capillary electrophoresis and Fourier transform infrared (FTIR) difference spectroscopic methods are used to characterize the nature of drug-DNA interaction and to determine the taxol binding site, the binding constant, sequence selectivity, helix stability and biopolymer secondary structure in the taxol-DNA complexes in vitro. Structural analysis showed that taxol is an external DNA binder with no affinity towards DNA intercalation. The major target of taxol is A-T, G-C bases and the backbone PO(2) groups. Two bindings were observed for taxol-DNA complexes with K(1)= 1.4 x 10(4) M(-1) and K(2)=3.5 X 10(3) M(-1). The taxol-DNA interaction is associated with a partial helix stabilization and no major alterations of B-DNA structures.
authors.affiliation: Department of Chemistry-Biology, University of Québec at Trois-Rivières, C.P. 500, (Québec) Canada G9A 5H7.
authors.forename: H
authors.initials: H
authors.lastname: Malonga
authors.forename: J F
authors.initials: JF
authors.lastname: Neault
authors.forename: S
authors.initials: S
authors.lastname: Diamantoglou
authors.forename: H A
authors.initials: HA
authors.lastname: Tajmir-Riahi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019075:Electrophoresis, Capillary; D009690:Nucleic Acid Conformation / Q000187:drug effects; D017239:Paclitaxel / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004247:DNA; C427203:calf thymus DNA; D017239:Paclitaxel