title: An optimized polyamine moiety boosts the potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512.
abstract: Combined computational-experimental analyses explain and quantify the spermine-vectorized F14512's boosted potency as a topoII poison. We found that an optimized polyamine moiety boosts drug binding to the topoII/DNA cleavage complex, rather than to the DNA alone. These results provide new structural bases and key reference data for designing new human topoII poisons.
authors.affiliation: Laboratory of Molecular Modeling and Drug Discovery, Istituto Italiano di Tecnologia, Via Morego 30, 16163 Genoa, Italy. marco.devivo@iit.it.
authors.forename: Giulia
authors.initials: G
authors.lastname: Palermo
authors.forename: Elirosa
authors.initials: E
authors.lastname: Minniti
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Greco
authors.forename: Laura
authors.initials: L
authors.lastname: Riccardi
authors.forename: Elena
authors.initials: E
authors.lastname: Simoni
authors.forename: Marino
authors.initials: M
authors.lastname: Convertino
authors.forename: Chiara
authors.initials: C
authors.lastname: Marchetti
authors.forename: Michela
authors.initials: M
authors.lastname: Rosini
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
authors.forename: Anna
authors.initials: A
authors.lastname: Minarini
authors.forename: Marco
authors.initials: M
authors.lastname: De Vivo
mesh_terms: D004247:DNA / Q000378:metabolism; D053837:DNA Cleavage / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013096:Spermine / Q000737:chemistry* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C534191:F14512; D059005:Topoisomerase II Inhibitors; D013096:Spermine; D004247:DNA; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin