. . "2015-12-31+01:00"^^ . "1"^^ . "2012-01-01+01:00"^^ . . "Interactions of organometallic antitumor compounds with nucleic acids and proteins: study of sequence and substrate selectivity"@en . . "1"^^ . "GAP208/12/0622" . "http://www.isvav.cz/projectDetail.do?rowId=GAP208/12/0622"^^ . . "6"^^ . . . "6"^^ . . "oxaliplatin RAPTA complexes nucleic acids proteins sequence dependance binding specificity"@en . "V sou\u010Dasnosti existuje siln\u00E1 popt\u00E1vka po protin\u00E1dorov\u00FDch l\u00E9\u010Divech, kter\u00E9 by byly v\u00EDce \u00FA\u010Dinn\u00E9 a m\u00E9n\u011B toxick\u00E9 ne\u017E cisplatina. Mechanismus \u00FA\u010Dinku cisplatiny a p\u0159\u00EDbuzn\u00FDch l\u00E9\u010Div spo\u010D\u00EDv\u00E1 p\u0159edev\u0161\u00EDm v jejich vazb\u011B na DNA. Ta vede ke zm\u011Bn\u011B struktury DNA a zm\u011Bn\u011B jej\u00EDch interakc\u00ED s proteiny. Tento projekt bude zam\u011B\u0159en na vazbu n\u00E1sleduj\u00EDc\u00EDch komplex\u016F na DNA: (1) oxaliplatinu, (2) RAPTA-B komplex a (3) Os(II) a Rh(III) analogy RAPTA complex\u016F. DNA bude v prvn\u00EDm kroku reprezentov\u00E1na pomoc\u00ED ds(pGpG) dinucleotidu, v dal\u0161\u00EDm kroku bude zahrnut je\u0161t\u011B i vedlej\u0161\u00ED p\u00E1r baz\u00ED. Pomoc\u00ED DFT a ab initio metod z\u00EDsk\u00E1me informace na molekul\u00E1rn\u00ED \u00FArovni, kter\u00E9 nejsou k dispozici z experiment\u016F, zvl\u00E1\u0161t\u011B data o (de)stabilizaci tranzitn\u00EDch stav\u016F a jejich z\u00E1vislosti na sekvenci, data o pr\u016Fb\u011Bhu lok\u00E1ln\u00EDch zm\u011Bn v sekund\u00E1rn\u00ED struktu\u0159e DNA b\u011Bhem vazby komplex\u016F a data o vlivu nav\u00E1zan\u00E9ho komplexu na p\u00E1rov\u00E9 interakce. U uva\u017Eovan\u00FDch komplex\u016F bude tak\u00E9 vypo\u010D\u00EDt\u00E1na vazebn\u00E1 selektivita vzhledem k protein\u016Fm." . . . . "2014-04-18+02:00"^^ . . "At present there is a strong request for more potent and less toxic anticancer drugs than cisplatin. The mode of action of cisplatin and related drugs includes a binding to DNA as a key step of their antitumor activity. It leads to a modification of DNA structure and changes of its interactions with proteins. We will focus on the binding of the following complexes to DNA: (1) oxaliplatin, (2) RAPTA-B complex and (3) Os(II) and Rh(III) analogues of RAPTA complexes. DNA will be represented by ds(pGpG) dinucleotide in the first step, in the second step flanking bases will be also included. Using DFT and ab initio methods we will obtain information on the molecular level which are not available from experimental results, especially data on transition states' (de)stabilizations and their sequence dependence, course of local changes in the secondary structure of DNA during the drug coordination, influence of the complex binding on the base-pair interactions. The drug-binding selectivity towards proteins as the second possible targets in cells will be also evaluated."@en . "2015-04-23+02:00"^^ . . . . "Interakce organokovov\u00FDch protin\u00E1dorov\u00FDch komplex\u016F s nukleov\u00FDmi kyselinami a proteiny: studium sekven\u010Dn\u00ED a substr\u00E1tov\u00E9 selektivity" . "0"^^ . . .