TAILIEUCHUNG - Báo cáo khoa học: Deoxyribonuclease I footprinting reveals different DNA binding modes of bifunctional platinum complexes

Deoxyribonuclease I (DNase I) footprinting methodology was used to analyze oligodeoxyribonucleotide duplexes containing unique and single, site-specific adducts of trinuclear bifunctional platinum compound, [{trans-PtCl(NH3 )2}2l-trans-Pt(NH3 )2{H2N(CH2 )6NH2}2 ] 4+ (BBR3464) and the results were compared with DNase I footprints of some adducts of con-ventional mononuclearcis-diamminedichloroplatinum(II) (cisplatin). | ềFEBS Journal Deoxyribonuclease I footprinting reveals different DNA binding modes of bifunctional platinum complexes Katerina Chválová1 Jana KaSparkova1 Nicholas Farrell2 and Viktor Brabec1 1 Institute of Biophysics Academy of Sciences of the Czech Republic Brno Czech Republic 2 Department of Chemistry Virginia Commonwealth University Richmond USA Keywords cross-link conformation DNA DNase I footprinting platinum complex Correspondence V. Brabec Institute of Biophysics Academy of Sciences of the Czech Republic Kralovopolska 135 CZ-61265 Brno Czech Republic Fax 420 51412499 Tel 420 541517148 E-mail brabec@ Website http labs BNAIAD These authors contributed equally to this work. Received 25 April2006 revised 1 June 2006 accepted 1 June 2006 Deoxyribonuclease I DNase I footprinting methodology was used to analyze oligodeoxyribonucleotide duplexes containing unique and single site-specific adducts of trinuclear bifunctional platinum compound trans-PtCl NH3 2 2p-trans-Pt NH3 2 H2N CH2 6NH2 2 4 BBR3464 and the results were compared with DNase I footprints of some adducts of conventional mononuclear cis-diamminedichloroplatinum II cisplatin . These examinations took into account the fact that the local conformation of the DNA at the sites of the contacts of DNase I with DNA phosphates such as the minor groove width and depth sequence-dependent flexibility and bendability of the double helix are important determinants of sequencedependent binding to and cutting of DNA by DNase I. It was shown that various conformational perturbations induced by platinum binding in the major groove translated into the minor groove allowing their detection by DNase I probing. The results also demonstrate the very high sensitivity of DNase I to DNA conformational alterations induced by platinum complexes so that the platinum adducts which induce specific local conformational alterations in DNA are differently recognized by DNase I. doi DNA .

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