Dr. Joe Bradshaw

Porphyrin Interaction with DNA

Research in the group involves the synthesis of neutral "tentacle" water-soluble porphyrins to be tested as possible intercalators of DNA.  Metalloporphyrins of this nature have been shown to be tumor specific and thus have potential as possible tumor therapy agents. It has been recently demonstrated that the synthesis of these neutral porphyrins containing poly-alcohol functionalities to achieve water-solubility can be carried out (Figure 1). Characterization of these materials using standard techniques of IR and NMR are carried out.  The rational for the proposed investigation is that the cationic natures of the porphyrins that have been studied thus far (+2 to +4) most probably influence DNA binding due to charge considerations alone.  Furthermore, by utilizing neutral water-soluble porphyrins, changing the metal (M = Ni²⁺, Zn²⁺, Cu²⁺, Mn³⁺, Fe³⁺, Co³⁺) within the porphyrin core can provide insight into question of the metal center/oxidation state role in DNA binding.  Investigation of these porphyrin / DNA interactions initially will be studied by HPLC (High Performance Liquid Chromatography). The specific interaction of these new metalloporphyrins and a “hair-pin” oligonucleotide will be studied using polyacrylamide gel electrophoresis, PAGE, to determine whether inside/outside binding or cleavage of the oligonucleotide occurs.  This project will provide preliminary evidence into the ability of these novel water-soluble porphyrins to interact with DNA bases.  This research is funded by a J. D. Patterson Grant.

Figure 1