Novel Supramolecular cylinders and their interaction with DNA probing effects o...
Novel Supramolecular cylinders and their interaction with DNA probing effects of cylinder structure and targeting DNA junctions
The scientific aim of this proposed project is to understand what features of nanoscale synthetic cylinders, and which biomolecular binding mode, give rise to the observed biological effects on the cell cycle and to probe the mech...
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Descripción del proyecto
The scientific aim of this proposed project is to understand what features of nanoscale synthetic cylinders, and which biomolecular binding mode, give rise to the observed biological effects on the cell cycle and to probe the mechanism and temporal relationships of that action in more detail. Our hypothesis is that the cylinder recognition of Y-shaped junctions, particularly replication forks, is a key feature of their action. The new design strategies will create cylinders which deconvolute the two different DNA binding modes (Y-shaped junction or major groove) and are founded on careful analysis of the X-ray structure of the 3 way junction and an NMR structure of the major groove binding: the designs add functionality to prevent one of these two binding modes while permitting the other. Within each overall design strategy, a number of different cylinders are proposed and, as detailed, the results of the biophysical and cell delivery studies will be used to optimise the design and select the most suited.