Fri, Sep. 30, 2016, 4:30pm - 6:00pm
Carl Icahn Laboratory, Room 101
Host: Tom Muir
Biocompatible photooxygenation catalyst that targets amyloid aggregation
Aggregation of peptide/protein is intimately related to a number of human diseases. More than twenty have been identified to aggregate into fibrils containing extensive b-sheet structures, and species generated in the aggregation processes (i.e., oligomers, protofibrils, and fibrils) contribute to disease development. Amyloid-b peptide (designated Ab), related to Alzheimer disease (AD), is the representative example. Artificial chemical transformation of toxic, aberrant Ab to less toxic forms at the disease site might be a new candidate for AD treatment. Thus, covalent installation of hydrophilic oxygen atoms to Ab using aerobic oxygen and visible light as oxygen atom- and energy sources, respectively, in the presence of a catalyst (i.e., catalytic photooxygenation) was used. Selective, cell-compatible photo-oxygenation of Aβ by a flavin catalyst attached to an Aβ-binding peptide markedly decreased aggregation potency and neurotoxicity of Aβ. Furthermore, we designed photooxygenation catalysts that can be turned on only when binding with the higher-order structures of amyloid aggregates. This on/off switchable activity of the catalyst that senses amyloid structure enabled highly Ab-selective oxygenation in the presence of other bioactive peptides and living cells.