SPERMINE BINDING TO GC-RICH DNA - EXPERIMENTAL AND THEORETICAL-STUDIES

The DNA binding of spermine has been studied using experimental and co mputational approaches. Spermine blocks 5'-GC interstrand crosslinking by a,5-diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTC CAAGATGCATCAGATG 5'-CATCTGATGCATC-TTGGAAG (where the underlined nucleo tide bases represent the crosslinking site). Molecular dynamics simula tions suggest that this is a result of preferential spermine binding a t the 5'-GC major groove site of the oligonucleotide. A further simula tion with a GC-alternating sequence shows a similar preference for the 5'-GC step. In a simulation including multiple spermine molecules, oc cupation of alternate 5'-GC steps occurred. From this, we deduce a mec hanism for the experimentally observed cooperativity of spermine bindi ng to poly(dGdC)(2). (C) 1996 Academic Press, Inc.