Neurodegenerative protein aggregation inhibition methods and compounds
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsIsabella A. Graef, Gerald R. Crabtree, Jason E. Gestwicki
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Abstract
Methods and compositions are provided for reducing aggregation of neurodegenerative proteins associated with neurotoxicity or other proteins. The compounds comprise a first domain or targeting element for binding to the target proteins linked to a second domain or recruiting element that binds to an aggregation inhibiting protein, e.g. a prolyl isomerase. By associating the aggregating forming proteins or neuronal cells under conditions where aggregating proteins are produced with the compound and the aggregation inhibiting protein, aggregation is reduced. The subject agents can be used in assays, investigating the etiology of the neuronal diseases and for prophylaxis and therapy.
Claims10
A method for diminishing the presence of a protein aggregate in an in vitro environment that includes said protein aggregate and an aggregation diminishing protein, said method comprising:
- a. introducing into said environment a compound having the structure:
- R1—L-R2
- wherein R1 is a first domain which binds to said protein aggregate and wherein R1 is Congo red;
- L is a single bond or a linking group of about 1 to 12 atoms in length;
- R2 is a second domain which binds to said aggregation diminishing protein and wherein R2 is selected from the group consisting of SLF, FK506, rapamycin, and ascomycin;
- and wherein said aggregation diminishing protein is an enzyme or heat shock protein;
- and
- b. incubating said compound in said environment for a period of time and temperature sufficient to diminish therein the presence of the protein aggregate.
Dependencies are inferred from the claim text.