Patent ID: 7345022

Claim:
A compound for inhibiting the toxicity of an amyloid protein or amyloid peptide, wherein the amyloid protein or amyloid peptide comprises an aggregation-inducing sequence of at least four modified or unmodified amino acids; said compound comprising a peptidyl sequence selected from the group consisting of: X aa1 —Y AA1 —X aa2 —Y AA2 —(S) n ; (S) n —X aa1 —Y AA1 —X aa2 —Y AA2 ; Y AA1 —X aa1 —Y AA2 —X aa2 —(S) n ; (S) n —Y AA1 —X aa1 —Y AA2 —X aa2 ; X aa1 —Y AA1 —X aa2 —Y AA2 —X aa3 —(S) n ; (S) n —X aa1 —Y AA1 —X aa2 —Y AA2 —X aa3 ; Y AA1 —X aa1 —Y AA2 —X aa2 —Y AA3 —(S) n ; (S) n —Y AA1 —X aa1 —Y AA2 —X aa2 —Y AA3 ; X aa1 —Y AA1 —X aa2 —Y AA2 —X aa3 —Y AA3 —(S) n ; (S) n —X aa1 —Y AA1 —X aa2 —Y AA2 —X aa3 —Y AA3 ; Y AA1 —X aa1 —Y AA2 —X aa2 —Y AA3 —X aa3 —(S) n ; and (S) n —Y AA1 —X aa1 —Y AA2 —X aa2 —Y AA3 —X aa3 ; wherein: (a) X aa1 , X aa2 , and X aa3 are natural or synthetic amino acids that are identical or homologous to alternating amino acids of the aggregation-inducing sequence of the amyloid protein or amyloid peptide, and that have side chains adapted for cross-strand side chain interactions with a β-sheet; (b) Y AA1 , Y AA2 , and Y AA3 are natural or synthetic amino acids that are identical or homologous to alternating amino acids of the aggregation-inducing sequence of the amyloid protein or amyloid peptide; wherein Y AA1 , Y AA2 , and Y AA3 correspond to amino acids that will be positioned on opposite faces of a β-sheet containing the amino acids that correspond to X aa1 , X aa2 , and X aa3 ; and wherein the amino acids in the amyloid protein or amyloid peptide that correspond to X aa1 , X aa2 , and X aa3 alternate with the amino acids in the amyloid protein or amyloid peptide that correspond to Y AA1 , Y AA2 , and Y AA3 ; wherein at least two of Y AA1 , Y AA2 , and Y AA3 are C α,α -disubstituted amino acids; (c) (S) n is a hydrophilic region comprising hydrophilic amino acids or other hydrophilic groups; wherein n is from 4 to 10, and wherein said hydrophilic region has a size not larger than about the size of a decapeptide; (d) either or both ends of said peptidyl sequence optionally comprise additional functionality that does not adversely affect the compound's ability to inhibit the toxicity of an amyloid protein or amyloid peptide, as compared to an otherwise identical compound lacking such additional functionality; (e) the number of amino acids in the aggregation sequence of the amyloid protein or amyloid peptide may be the same as, or different from, the number of natural or synthetic amino acids in said peptidyl sequence; and (f) said compound is neither Lys-Dibg-Val-Dbzg-Phe-Dpg-(Lys) 6 -NH 2 (SEQ ID NO: 4); nor Dpg-Phe-Dbzg-Val-Dibg-(Lys) 7 -NH 2 (SEQ ID NO: 18); nor(Lys) 6 -Dibg-Val-Dbzg-Phe-Dpg-Lys-NH 2 (SEQ ID NO: 19).