| Popis: |
The interaction of small molecules with DNA is an area ofresearch which is important to several fields, for example in anti-cancer and anti-viral drug design. However, the physical processes behind such molecular associations and their resultant biological activity are unclear. A thorough understanding ofthe underlying thermodynamics which govern such binding processes will aid in the design ofnew DNA binding ligands with enhanced properties. In this thesis the DNA binding properties ofa new class ofpotential intercalating agents, the dihydro-imidazo-phenathridinium (DIP) ligands, are discussed. These DIP ligands are not as susceptible to physiological reduction as existing nitrogen heteroatomics and have properties that make them attractive candidates in a range ofbiomolecular proc'esses. For example, as anti-tumor agents and in DNA drug targeting applications. The versatility ofthese ligands allows the incorporatIon ofvarious features to potentially affect minor/major groove binding, inter-ehain interactions along with combinations ofthese. Isothermal titration calorimetry and differential scaiming calorimetry in addition to more indirect biophysical methods are used to characterise the thermodynamics, stoichiometry and modes ofbinding for this new family ofmolecules. |
