"0"^^ . . . "Projekt roz\u0161\u00ED\u0159il znalosti o retrovirov\u00FDch prote\u00E1z\u00E1ch d\u016Fle\u017Eit\u00FDch pro vznik nov\u00FDch funk\u010Dn\u00EDch virion\u016F. \u0158e\u0161itel\u00E9 identifikovali strukturu odpov\u011Bdnou za dimerizaci virem k\u00F3dovan\u00E9 prote\u00E1zy a pomoc\u00ED mutant\u016F zjistili jej\u00ED \u00FAlohu v aktivn\u00EDm centru enzymu. V\u00FDsledky"@cs . "Dimerisace retrovirov\u00FDch proteinas: charakterisace, vztah struktura-aktivita a inhibice" . . . . . . "http://www.isvav.cz/projectDetail.do?rowId=GA303/98/1559"^^ . "V\u0161echny proteiny retrovir\u016F jsou exprimov\u00E1ny ve form\u011B polyproteinov\u00FDch prekursor\u016F. Jejich specifick\u00E9 proteolytick\u00E9 \u0161t\u011Bpen\u00ED virovou proteinasou (PR) je nezbytn\u00E9 pro vznik zral\u00FDch, infek\u010Dn\u00EDch virov\u00FDch \u010D\u00E1stic. Retrovirov\u00E9 PR jsou tak atraktivn\u00EDm c\u00EDlem pro v\u00FDvoj virostatik. V\u0161echny retrovirov\u00E9 PR pat\u0159\u00ED do skupiny aspart\u00E1tov\u00FDch proteas a jsou aktivn\u00ED ve form\u011B dimeru. Pr\u00E1v\u011B dimerisace retrovirov\u00FDch PR je rozhoduj\u00EDc\u00ED pro regulaci a p\u0159esn\u00E9 na\u010Dasov\u00E1n\u00ED jejich aktivace v pr\u016Fb\u011Bhu \u017Eivotn\u00EDho cyklu retroviru. V p\u0159edkl\u00E1dan\u00E9m projektu navrhujeme prostudovat biochemick\u00E9 a fysik\u00E1ln\u011B chemick\u00E9 aspekty tohoto d\u011Bje. Navrhneme a p\u0159iprav\u00EDme serii nov\u00FDch fluorogenn\u00EDch substr\u00E1r\u016F retrovirov\u00FDch PR z n\u011Bkolika retrovir\u016F (HIV-l a 2, Mason-Pfizerova opi\u010D\u00EDho retroviru a viru hov\u011Bz\u00ED leuk\u00E9mie), ur\u010D\u00EDme kinetick\u00E9 a termodynamick\u00E9 parametry jejich dimerisace t\u011Bchto enzym\u016F. Podobnou studii navrhujeme prov\u00E9st na s\u00E9rii mutant\u016F HIV-1 PR, isolovan\u00FDch z virov\u00FDch kmen\u016F resistentn\u00EDch v\u016F\u010Di inhibitor\u016Fm PR s c\u00EDlem ov\u011B\u0159it, zda inhibitory dim" . "GA303/98/1559" . . . . "Dimerisation of retroviral proteinases: characterisation, structure-activity and inhibition study"@en . "All retroviral proteins are expressed as polyprotein precursors. Specific proteolytic cleavage by viral aspartic proteinase ( PR ) is required for the formation of mature, infectious particles. Retroviral PRs are thus an attractive target for antiviral chemotherapy. All retroviral PRs are active as dimers. The dimerisation of retroviral PRs is a crucial step for the regulation and correct timing of their activity during the retroviral life cycle. In the proposed project we plan to study biochemical andchemical aspects of this process. We will design and prepare a series of novel fluorogenic substrates of retroviral PRs from several retroviruses ( HIV-1 and -2, Mason-Pfizers monkey retrovirus and bovine leukemia virus ), determine kinetic and thermodynamic parameters of their dimerisation and design and test specific inhibitors of the dimerisation of these inhibitors. We also propose to perform a similar study on a series of mutants of HIV-1 PR isolated from viral strains resistant towards th"@en . "1"^^ . . "3"^^ . . "0"^^ . . "3"^^ . .