Photodynamic Therapy (PDT) is the treatment of disease with photoactivated chemotherapeutics. Most often, PDT involves the formation of singlet oxygen via energy transfer from dye sensitizers. Singlet oxygen is a highly reactive, and relatively unselective, active agent. Also, the sensitizer remains in the patient's system producing sensitivity to bright light that can persist for weeks. The long-term goal of this project is the development of a new photodynamic therapy system that does not utilize singlet oxygen and does not leave a patient sensitive to light. The achievement of this long-term goal requires the development of new chemistry and biochemistry for the photochemical production of biologically active molecules.
The specific aims of this proposal are: I. To develop a system capable of acting as a photolabile amine protecting group that utilizes visible light. II. To achieve general in-vitro photoactivation of enzymes. III. To photoactivate thrombin and TPA, enzymes of ophthalmological relevance, using visible light. IV. To develop photochemistry capable of photoreleasing biologically active aldehydes and an in vitro demonstration of biological activity dependent on visible light. The rationale behind these aims are two fold. The first is the idea that photoactive agents that possess a more selective biological activity will provide a more predictable response in PDT and allow the tailoring of PDT agents to specific diseases. For example, a clot busting enzyme that could be photoactivated could form the basis of an effective treatment for Central Retinal Vein Occlusion, which currently has no treatment. Or the photoactivation of an anti-viral agent would allow the treatment of a number of dermal viral infections. An effective general photoactivation scheme for biomolecules could have limitless applications in the treatment of disease. The project will involve the investigation of anthraquinone photochemistry for the photodeprotection of amines and aldehydes, the investigation of this photochemistry in the photoactivation of enzymes, and an assay of the photobiological activity of caged biocides and caged virucides.
| Jones, Paul B; Brinson, Robert G; Sarma, Saurav J et al. (2008) Observation of heavy atom effects in the development of water soluble caged 4-hydroxy-trans-2-nonenal. Org Biomol Chem 6:4204-11 |
| Oates, R P; Jones, Paul B (2008) Photosensitized tetrahydropyran transfer. J Org Chem 73:4743-5 |
| Zuidema, Daniel R; Jones, Paul B (2005) Photochemical relationships in Sacoglossan polypropionates. J Nat Prod 68:481-6 |
| Brinson, Robert G; Jones, Paul B (2004) Caged trans-4-hydroxy-2-nonenal. Org Lett 6:3767-70 |
