Structure-based peptide inhibitors of alpha-synuclein aggregation
AssigneeThe Regents of the University of California
InventorsDavid S. Eisenberg, Smriti Sangwan, Lin Jiang
Life of this patent
Estimating the term…
Abstract
This invention relates to inhibitory peptides which bind to α-synuclein molecules and inhibit α-synuclein amyloidogenic aggregation, α-synuclein cytotoxicity, and spread of α-synuclein. Methods of making and using the inhibitory peptides (e.g. to treat subjects having conditions or diseases that are mediated by α-synuclein, such as Parkinson's disease, dementia with Lewy bodies, or MSA) are described.
Claims22
A composition of matter comprising at least one inhibitory peptide that inhibits α-synuclein (SEQ ID NO:
- 1) aggregation by binding to residues 68-78 of α-synuclein;
- wherein:
- (a) the inhibitory peptide comprises the sequence:
- (SEQ ID NO:
- 3)
- GAVVWGVTAVKK;
- or
- (SEQ ID NO:
- 4)
- RAVVTGVTAVAE;
- and
- at least one of the amino acids in the inhibitory peptide comprises a non-naturally occurring amino acid;
- and/or
- the inhibitory peptide is coupled to a heterologous peptide tag.
(canceled)
A method of observing the presence or absence of α-synuclein amyloid fibrils in a biological sample comprising:
- (a) combining a biological sample with a peptide that binds to residues 68-78 of α-synuclein;
- (b) allowing the peptide to bind to α-synuclein amyloid fibrils that may be present in the biological sample;
- and
- monitoring combination (b) for the presence of complexes formed between α-synuclein amyloid fibrils and the peptide;
- wherein the presence of said complexes show the presence of α-synuclein amyloid fibrils in the biological sample by MRI or PET, or other imaging method.
A modified peptide comprising a peptide selected from
- (SEQ ID NO:
- 3)
- GAVVWGVTAVKK;
- and
- (SEQ ID NO:
- 4)
- RAVVTGVTAVAE;
- and
- wherein at least one of the amino acids in the peptide comprises at least one methylated amino acid residue.
22-23. (canceled)
Dependencies are inferred from the claim text.