The perfect anticancer drug would kill cancer cells without causing any harm to the surrounding healthy tissues. That ideal medicine is searched for in this thesis, in the form of a ruthenium... Show moreThe perfect anticancer drug would kill cancer cells without causing any harm to the surrounding healthy tissues. That ideal medicine is searched for in this thesis, in the form of a ruthenium coordination complex.Metal complexes are known to interact with DNA in several different modes, amongst which are coordination, intercalation of the aromatic part of the molecule between the DNA base-pairs and binding of the complex to one of the DNA grooves.Is there a correlation between the ruthenium–DNA interactions and the cytotoxicity of these complexes? Three ruthenium polypyridyl complexes (1a-c) were synthesized and characterized, which can coordinate to guanine. The structure-related 1e and 1f, as well as the dinuclear complex 1g, were also chosen for these studies. The interactions between each ruthenium complex and DNA were studied; the activities of the compounds in different cancer cells were tested.The results of these tests suggest that 1a-c and 1e coordinate to DNA, while 1g probably fits in the DNA groove. These complexes display moderate activity in some cancer cell lines. The inactive complex 1f can coordinate to guanine and bind to DNA via intercalation or groove-binding. 1f is the only one of the studied compounds that lacks an azo group, which suggests that this group is essential for cytotoxicity.The interactions between metal complexes and other biological molecules are also mentioned. Show less
The work described in this thesis deals with characterization of DNA binding by the BRCT domain of the large subunit of RFC. Replication Factor C (RFC) is a five protein complex involved in... Show moreThe work described in this thesis deals with characterization of DNA binding by the BRCT domain of the large subunit of RFC. Replication Factor C (RFC) is a five protein complex involved in initiating and regulating new DNA synthesis. The first half of the thesis describes region of the RFC and structural determinants of DNA required for productive protein-DNA interaction. The second half describes three-dimensional structure determination of the protein-DNA complex, which consists of the BRCT region of the RFC and doubled stranded DNA. The resulting structure based on the data from NMR and mutagenesis reveals structural conservations of few amino acids among the members of BRCT domain superfamily, which are known to bind either phosphorylated peptide or DNA. The work may help us to identify other potential DNA binding BRCT domains. Show less
