. "Byly zji\u0161t\u011Bny unik\u00E1tn\u00ED rysy modifikace DNA nov\u00FDm cytostatikem BBR3464, jejich rozli\u0161en\u00ED bun\u011B\u010Dn\u00FDmi proteiny a opravy. Porozum\u011Bn\u00ED t\u011Bmto nov\u00FDm interakc\u00EDm umo\u017En\u00ED pln\u00E9 vyu\u017Eit\u00ED klinick\u00E9ho potenci\u00E1lu t\u00E9to nov\u00E9 t\u0159\u00EDdy platinov\u00FDch cytostatik."@cs . . "2014-02-12+01:00"^^ . "DNA; cancer; cytostatics; antitumor activity; platinum"@en . . "14"^^ . "14"^^ . . . "Molecular mechanisms underlying anticancer effects of a new drug BBR3464"@en . "Tento projekt navrhuje studovat unik\u00E1tn\u00ED rysy aduktu vytvo\u0159en\u00FDch na DNA polynukle\u00E1rn\u00EDmi platinov\u00FDmi slou\u010Deninami z hlediska biologick\u00FDch d\u016Fsledk\u016F tvorby t\u011Bchto nov\u00FDch struktur. Tyto nov\u00E9 slou\u010Deniny, ve kter\u00FDch jsou dv\u011B nebo t\u0159i platinov\u00E9 koordina\u010Dn\u00ED jednotky spojeny line\u00E1rn\u00EDm m\u016Fstkem, p\u0159edstavuj\u00ED d\u016Fle\u017Eitou novou t\u0159\u00EDdu l\u00E9\u010Div proti rakovin\u011B. Prvn\u00ED l\u00E1tka ozna\u010Dovan\u00E1 BBR3464 je nyn\u00ED ve f\u00E1zi II klinick\u00E9ho zkou\u0161en\u00ED na pacientech posti\u017Een\u00FDch rakovinou. Budeme identifikovat a pop\u00ED\u0161eme unik\u00E1tn\u00ED rysy modifikac\u00ED DNA cytostatikem BBR3464 v\u010Detn\u011B preasociace elektricky nabit\u00E9ho farmaka s cukr-fosf\u00E1tovou p\u00E1te\u0159\u00ED DNA, m\u016Fstky dlouh\u00E9ho dosahu, ve kter\u00FDch m\u00EDsta vazby komplexu BBR3464jsou separov\u00E1na a\u017E \u010Dty\u0159mi intervenuj\u00EDc\u00EDmi p\u00E1ry b\u00E1z\u00ED, konforma\u010Dn\u00ED flexibility a podstaty nevratn\u00FDch konforma\u010Dn\u00EDch zm\u011Bn vyvolan\u00FDch v kanonick\u00FDch struktur\u00E1ch DNA a jejich d\u016Fsledky pro rozli\u0161en\u00ED bun\u011B\u010Dn\u00FDmi proteiny a nukleotidovou excisn\u00ED opravu." . " antitumor activity" . . "1"^^ . "This project proposes to study the unique aspects of the DNA adducts formed by the polynuclear platinum compounds and to relate formation of these novel structures to their biological consequences. These compounds, where two or three platinum coordination units are linked in a linear fashion, comprise an important new class of anticancer drugs. The first clinical compound, currently denoted BBR3464, is a trinuclear, bifunctional DNA binding agent, which is now in Phase II clinical trials in cancer patients. We will identify and describe unique features of DNA binding mode of BBR3464 including pre-association of the charged drug on the DNA polymer backbone, long-range intra- and interstrand cross-links where the sites of platination are separated by up to four intervening base pairs, the conformational flexibility and the nature of the irreversible conformational changes induced in canonical DNA structures and their consequences for protein recognition and nucleotide excision repair."@en . . "http://www.isvav.cz/projectDetail.do?rowId=KJB5004301"^^ . "0"^^ . "DNA" . . "0"^^ . "Molekul\u00E1rn\u00ED mechanismy protin\u00E1dorov\u00E9ho p\u016Fsoben\u00ED nov\u00E9ho l\u00E9\u010Diva BBR3464" . " cancer" . . . . . . "Unique aspects of DNA modifications by a new anticancer drug, BBR3464, their recognition by cellular proteins and repair were determined. Understanding these interactions will make it possible to exploit the full clinical potential of these new agents."@en . . . . . . . . "KJB5004301" . " cytostatics" . .