The compatibility of molecular structures of Di phenyl diamines drugs with minor groove of DNA and the importance of cationic amidine group in DNA binding

The binding of Diphenyl diamine drugs within the minor groove of DNA has been investigated by using force field and ab initio MO methods. Four drugs of different molecular sizes are taken to examine the compatible sizes of drugs for binding within minor groove of DNA. It is one of the essential characteristic of minor groove binding drugs. In addition the energetic of cationic amidine group in DNA binding is also analysed to differentiate the dominating factors for minor groove binding. The crescent sized molecules that fit to the minor groove of DNA can bind effectively within the minor groove. The role of cationic amidine groups of these drugs in DNA binding is significant. These charged groups interact with various atomic sites present within minor groove. The formation of stable drug-DNA complexes depends on the types of intermolecular hydrogen bonds formed in the complexes. The hydrogen bonds between amidine groups of drugs and thymine nucleobase can stabilize the drug within AT sequences, and it is one of the reasons for AT sequence selectivity of this drug.