title: Further insight into the DNA recognition mechanism of trabectedin from the differential affinity of its demethylated analogue ecteinascidin ET729 for the triplet DNA binding site CGA.
abstract: Trabectedin and its N12-demethylated analogue ET729 bind covalently to the central guanine of selected DNA triplets. Although both drugs equally target several sites, including AGA, we show that covalent modification of CGA is only achieved by ET729. By means of molecular dynamics simulations of the precovalent complexes, we explain in atomic detail how such a simple structural modification brings about this notable change in the DNA-binding selectivity profiles of these two drugs.
authors.affiliation: Departamento de Farmacología, Universidad de Alcalá, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Marco
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: David-Cordonnier
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
authors.forename: Carmen
authors.initials: C
authors.lastname: Cuevas
authors.forename: Federico
authors.initials: F
authors.lastname: Gago
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004149:Dioxoles / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000737:chemistry*; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C100350:ecteinascidin 729; D004247:DNA; D000077606:Trabectedin