Cyclized transthyretin peptide and methods of use therefor
AssigneeWisconsin Alumni Research Foundation
InventorsREGINA M. MURPHY, Patricia Y. Cho, Jeffrey A. Johnson, Xiaomeng Lu
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Abstract
The present disclosure describes cyclized peptides that inhibit Aβ toxicity and therefore can be used as therapeutic agents to treat Alzheimer's Disease.
Claims25
A cyclized peptide comprising the sequence SKVVTPPRYTIAALLSPYSYSQ (SEQ ID NO:
- 1) or a variant thereof as defined herein.
A composition of matter comprising (i) a cyclized peptide comprising the sequence SKVVTPPRYTIAALLSPYSYSQ (SEQ ID NO:
- 1), or a variant thereof as defined herein, wherein said terminal S or T and Q residues are covalently bonded to each other, and (ii) a pharmaceutical buffer, carrier, diluent or excipient.
A method of producing a cyclized peptide comprising the sequence SKVVTPPRYTIAALLSPYSYSQ (SEQ ID NO:
- 1), or a variant thereof as defined herein, wherein said terminal S or T and Q residues are covalently bonded to each other, said method comprising the steps of:
- (a) coupling Fmoc-D-Glu-ODmab to a resin through the unprotected side chain;
- (b) assembling the peptide backbone using standard solid-phase synthesis;
- (c) deprotecting the Dmab protecting group;
- (d) performing on-resin cyclization with benzotriazol-1-yl-N-oxy-tris(pyrrolidino)-phosphonium hexafluorophosphate;
- and
- (e) cleaving peptide from resin using a cleavage cocktail.
A method of protecting neurons from Aβ toxicity in a subject comprising administering to said subject a cyclized peptide comprising the sequence SKVVTPPRYTIAALLSPYSYSQ (SEQ ID NO:
- 1), or a variant thereof as defined herein.
Dependencies are inferred from the claim text.