Discordant helix stabilization for prevention of amyloid formation
First Claim
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1. A method of decreasing the rate of formation of β
- -strand structures between at least two discordant helix-containing polypeptides, the method comprising contacting the discordant helix-containing polypeptides with a dipolar tripeptide that stabilizes an α
-helical form of at least one discordant helix, wherein the dipolar tripeptide stabilizes an α
-helical form of at least one discordant helix, thereby decreasing the rate of formation of β
-strand structures between the discordant helix-containing polypeptides, and wherein the discordant helix-containing polypeptides are each independently Aβ
peptides.
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Abstract
The invention is based on the discovery that the presence of a discordant helix in a protein or peptide is predictive of that protein or peptide'"'"'s ability to form amyloid. The invention includes methods for detecting discordant helices and methods of screening for compounds that stabilize the α-helix of a discordant helix-containing polypeptide. Compounds discovered using these methods are useful for treating or preventing disorders in which amyloid is produced. Such disorders include Alzheimer'"'"'s disease and prion-associated disorders.
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7 Claims
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1. A method of decreasing the rate of formation of β
- -strand structures between at least two discordant helix-containing polypeptides, the method comprising contacting the discordant helix-containing polypeptides with a dipolar tripeptide that stabilizes an α
-helical form of at least one discordant helix, wherein the dipolar tripeptide stabilizes an α
-helical form of at least one discordant helix, thereby decreasing the rate of formation of β
-strand structures between the discordant helix-containing polypeptides, and wherein the discordant helix-containing polypeptides are each independently Aβ
peptides. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- -strand structures between at least two discordant helix-containing polypeptides, the method comprising contacting the discordant helix-containing polypeptides with a dipolar tripeptide that stabilizes an α
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