A broad range of compounds target DNA as part of their therapeutic mechanism. The antiparasitic properties of clinically useful heterocyclic diamidines are correlated with their DNA interactions. It is clear, however, that simple binding affinity does not explain the biological effects. Other features of these complexes, such as changes in DNA conformation, must be involved in the activity of specific compounds. The atomic force microscope (AFM) is a powerful tool to image small quantities of DNA, either with or without ligands. Although qualitative differences among samples may be discerned, the changes that can be obtained from a quantitative approach provide much more desirable information. We have implemented novel software to monitor changes in DNA contour length from multiple images in order to determine which compounds cause the greatest deviation in DNA contour length. This software allows user-defined coordinates to perform quantitative analysis. The effects of diamidines on biological DNA have been analyzed.

This research is funded by the National Institutes of Health, The Bill and Melinda Gates Foundation, and the Georgia Research Alliance.