Rose, who earned his Ph.D. this year, has been working on the project since 2004. He began by replacing the iron atom in a synthetic model of the enzyme with a different metal, ruthenium.
"Iron complexes are good in nature because they are highly reactive, but if you're trying to make a drug you want something that's more stable," Rose said. "The ruthenium complexes are much more stable when dissolved in water."
The first ruthenium nitrosyls he made released nitric oxide only under ultraviolet light, so Rose spent several years developing ways to sensitize them to specific wavelengths of visible light that could be used in photodynamic therapy. He did this by attaching dye molecules, called chromophores, to the ruthenium complex.
To test the resulting compounds as potential drugs, the chemists teamed up with breast cancer researcher Lindsay Hinck, a professor of molecular, cell, and developmental biology at UCSC. Hinck and postdoctoral researcher Rebecca Marlow worked with Rose to test the dye-sensitized ruthenium nitrosyls against breast cancer cells growing in tissue culture.
The unactivated compounds are fluorescent, which allowed the researchers to track them using a fluorescence microscope as the compounds were absorbed by the cancer cells. The release of nitric oxide after exposure to light quenched the fluorescence, and the cells showed signs of apoptosis within four to eight
Source: University of California, Santa CruzBack to HCB News