| The prodigiosins are a family of intensely red pigments produced as secondary metabolites by certain strains of the bacterial genus Serratia. These compounds possess antibacterial, cytotoxic, and T-cell immunosuppressive properties. Recently, we have shown prodigiosin, the parent member of this family, to facilitate spontaneous double-strand DNA cleavage in the presence of Cu(II). While the exact nature of the DNA damage is in question, the metal-coordination properties of prodigiosin have been proven vital to the observed nuclease event and were, therefore, a major focus of this research. It was found that the natural product coordinated Cu(II) in a 1:1 stoichiometry. However, mass spectrometry and X-ray crystallographic data suggested that the ligand had undergone oxidation as a solvent molecule was covalently attached to the ligand. Thus, it was hypothesized that the observed nuclease event may have been the result of Cu(II)-mediated DNA alkylation by prodigiosin. The results of the metal-coordination study of prodigiosin and several prodigiosin analogues will be presented.;Given the ability of prodigiosins to absorb light well into the visible region, coupled with their observed cytotoxicity, prodigiosins have been considered as potential photodynamic therapy agents. Our studies indicated that prodigiosin was much too cytotoxic in the absence of light to be utilized as a photodynamic therapy agent. However, several derivatives of the natural product were shown to display an encouraging ratio of light-induced cytotoxicity versus dark cytotoxicity. Therefore, the prodigiosins represent a novel family of compounds that could be developed as photosensitizing agents.;Recently, prodigiosin, through the possible covalent attachment of cystein-residues, was shown to be an effective tyrosine phosphatase inhibitor. Thus, the ability of prodigiosins to form covalent bonds with sulfur containing compounds may be vital to the observed inhibition. Our research has shown the prodigiosins to form stable adducts with various sulfur containing compounds. These adducts were characterized by HPLC-MS and NMR. The prodigiosins were also shown to form covalent adducts with biologically relevant nitrogen nucleophiles (DNA nucleotides) when activated by Cu(II) and 433 nm filtered light. The results of these investigations will be presented. |
