Cel Aim: To develop synthetic supramolecular agents that recognize DNA, to investigate the effects they have on the DNA structure and the potential for achieving these in a sequence selective manner Rationale and Summary: Natural biomolecule recognition of DNA relies primarily on non-covalent binding of large protein motifs to DNA. Supramolecular chemistry provides methodology for the design of large synthetic arrays of similar size and shape to such protein motifs. Such supramolecular non-covalent DNA binding agents will be designed and prepared and their DNA binding investigated. This will be achieved by preparing a synthetic library of supramolecular cylinders bearing different functional groups and combinations of groups on the surface and screening their DNA binding both for their effect on the DNA and for sequence selectivity. This will be achieved through the following objectives:1. Preparation of libraries of surface functionalized supramolecular cylinders2. Investigation of the DNA binding of the components of the library and estimation of binding strengths3. Investigation of the global structural effects on DNA induced by binding4. Investigation of sequence specificity of binding5. Optimization of cylinder design and functionality to achieve specific structural effects in a sequence specific manner. This multi-disciplinary project will provide me with advanced training in design and preparation of non-covalent DNA recognition agents (the expertise of Dr. Hannon), will enhance my expertise of circular dichroism and its application to DNA binding drugs and will extend this to give me new expertise in the technique of flow linear dicllroism for probing drug-DNA interactions (the expertise of Dr. Rodger) and in AFM imaging. Such an advanced trailing at the interface of Chemistry and Biology is facilitated by the complementary expertises of these two scientists who collaborate closely together and this makes Warwick the ideal place to gain such a training. In particular, expertise in flow linear dichroisru and its applications are restricted to only a few laboratories in the world and I hope to establish this technique in the Czech Republic on my return at the end of the fellowship. The range of training opportunities in both research and teaching available through the University of Warwick Academic Staff Development program will also be valuable in preparing and enabling me to establish a successful scientific research career on my return to the Czech Republic. Dziedzina nauki natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinssocial sciencespolitical sciencesgovernment systems Program(-y) FP5-HUMAN POTENTIAL - Programme for research, technological development and demonstration on "Improving the human research potential and the socio-economic knowledge base" (1998-2002) Temat(-y) Data not available Zaproszenie do składania wniosków Data not available System finansowania RGI - Research grants (individual fellowships) Koordynator UNIVERSITY OF WARWICK Wkład UE Brak danych Adres Gibbet Hill CV4 7AL COVENTRY Zjednoczone Królestwo Zobacz na mapie Koszt całkowity Brak danych
