Mass Spectrometry Studies of DNA-Directed Alkylating Agents

This work is focused on the use of Mass Spectrometry based technique to determine the site of drug binding and to observe the chemical reactions that occur during ligand-DNA interaction. Such approach is useful and has great potential in aiding DNA targeted drug design in terms of assessing the ligand DNA cross-linking ability, sequence specificity and to certain extent, degree of reactivity for a particular binding site. This work is part of a wider effort in developing drugs that target the minor groove region of the DNA which has been known to be invisible to DNA repair enzymes, a common problem that leads to cancer drug resistance. Mass spectrometry has many advantages in comparison to the conventional techniques applied in DNA targeted drug design. It can provide detail insights into the chemistry of drug-DNA interactions at high level of accuracy and sensitivity.