Complexes of DNA with minor groove binders: crystallographic studies

Abstract

This thesis describes the crystal structure determinations of ten minor groove binding ligands complexed to the DNA oligonucleotides d(CGCGAATTCGCGh and d(CGCAAATTTGCGh. The ligands are all based on bisbenzimidazole or bisquatemary ammonium heterocycles (BQAH) and some have additional DNA interacting functional groups. Two of the ligands presented in chapter 4 are models for DNA alkylators (nitrogen mustard and pyrrole diol) and their DNA bound structures confirm the reaction mechanisms for the true alkylating analogues. The other two ligands in this chapter are a carborane substituted bisbenzimidazole ligand and a BQAH molecule which contains no hydrogen bonding functionality. Neither ligand could be located in the crystal structures. yet the well defined DNA conformations showed that the ligands can bind in the minor groove of DNA.