Blood brain barrier permeation peptides
AssigneeWashington University
InventorsVijay Sharma, David Piwnica-Worms
Life of this patent
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Abstract
Novel blood-brain barrier permeant amyloid-targeting peptides and peptide conjugates are described. The peptide conjugates include a radioisotope or other label in a stable complex that translocates across brain capillary endothelial cell monolayers. The labeled peptide conjugate binds to amyloid plaques (Aβ) associated with Alzheimer's disease, and is useful for the targeted delivery of therapeutic and diagnostic molecules into the brain.
Claims38
A purified peptide, the amino acid sequence of which comprises SEQ. ID. NO.:
- 1.
A compound comprising a BBB-permeant, Aβ-targeting peptide coupled to a chelation core.
A method of detecting amyloid plaques in a living mammal, said method comprising coupling a medical imaging agent to a BBB permeant amyloid-targeting peptide conjugate.
A method of making a BBB permeant amyloid-targeting peptide conjugate labeled with a medical imaging agent, said method comprising synthesizing a BBB permeant amyloid-targeting peptide, the amino acid sequence of which comprises SEQ. ID. NO.:
- 1.
A method of making a BBB permeant amyloid-targeting peptide comprising:
- generating a small peptide library comprising a plurality of peptides wherein each peptide has a distinct amino acid sequence, each such sequence comprising a partial amino sequence from SEQ. ID. NO.:
- 2;
- testing each small peptide for amyloid-targeting specificity and BBB permeability;
- and
- comparing the amyloid-targeting specificity and BBB permeability of each small peptide to the amyloid-targeting specificity and BBB permeability of the peptide, the amino acid sequence of which comprises SEQ. ID. NO.:
- 1.
A composition, comprising a compound comprising:
- a BBB permeant peptide;
- a diagnostic or pharmacologically substance;
- and
- a linker moiety linking said peptide and said diagnostic or pharmacologically substance.
A kit, comprising a compound comprising:
- a BBB-permeant peptide;
- a metal chelation ligand;
- a linker moiety linking said peptide and said metal chelation ligand;
- and
- a reducing agent capable of reducing a metal that can be coordinately incorporated into said metal chelation ligand.
A method for imaging cells in vivo, comprising:
- administering to an animal a cell imaging effective amount of a compound comprising:
- a BBB-permeant peptide;
- a chelated radionuclide or a chelated relaxivity metal;
- and
- a linker moiety linking said peptide and said chelated radionuclide or said chelated relaxivity metal;
- and
- monitoring the location of said radionuclide or relaxivity metal within said animal.
Dependencies are inferred from the claim text.