title: Spermine binding to GC-rich DNA: experimental and theoretical studies.
abstract: The DNA binding of spermine has been studied using experimental and computational approaches. Spermine blocks 5'-GC interstrand crosslinking by 2,5-diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTCCAAGATGCATCAGATG 5'-CATCTGATGCATCTTGGAAG (where the underlined nucleotide bases represent the crosslinking site). Molecular dynamics simulations suggest that this is a result of preferential spermine binding at the 5'-GC major groove site of the oligonucleotide. A further simulation with a GC-alternating sequence shows a similar preference for the 5'-GC step. In a simulation including multiple spermine molecules, occupation of alternate 5'-GC steps occurred. From this, we deduced a mechanism for the experimentally observed cooperativity of spermine binding to poly(dGdC)2.
authors.affiliation: Department of Pharmaceutical Sciences, University of Southern California, Los Angeles 90033, USA.
authors.forename: M
authors.initials: M
authors.lastname: Yuki
authors.forename: V
authors.initials: V
authors.lastname: Grukhin
authors.forename: C S
authors.initials: CS
authors.lastname: Lee
authors.forename: I S
authors.initials: IS
authors.lastname: Haworth
mesh_terms: D001388:Aziridines / Q000494:pharmacology; D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D006873:Hydroquinones / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D013096:Spermine / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001388:Aziridines; D003432:Cross-Linking Reagents; D006873:Hydroquinones; D009838:Oligodeoxyribonucleotides; C084721:2,5-diaziridinylhydroquinone; D013096:Spermine; D004247:DNA