The discovery of new photoremovable protecting groups for rapid and efficient release of neurotransmitters, nucleotides, oligopeptides, and proteins is one of the primary goals of our research program. A series of inherently rapid photofragmentation reactions from the organic chromophore, p-hydroxyphenacyl (pHP), is employed to good advantage for the controlled release of bioactive substrates in biological environments. For example, the active site of PKA is switched off by reaction with p-hydroxyphenacyl bromide and switched back on by photolysis. Protected or "caged" substrates such as the p-hydroxyphenacyl derivatives of ATP, bradykinin, the active site of the C subunit of protein kinase A (seen here) and the neurotransmitters γ-glutamic acid and GABA have been employed for the controlled release of each of these substrates. Photolysis releases the nucleotide or protein with high efficiency and at rates that exceed 106s-1 to as high as 108s-1, much faster than any of the previously known caging derivatives. Much greater experimental control of the temporal, spatial, and concentration variables is now afforded for biologists, biochemists and physiologists who wish to study these bioactive substrates at their target sites.
Photochemical process for release of Bradykinin from pHP cage(left)......Caging and uncaging Glutathione(right)
Mechanism of Phototrigger
A second major thrust is the design and development of a new photoactivated cross-linking agent for lysine rich proteins. Tethered 1,n-diazo- and polyazopyruvates serve as the protein
Synthetic scheme for photostitching
last updated Jan 2005 by Rachel Moses