Amyloid beta peptide analogs and assemblies thereof
The present invention provides amyloid β peptide assemblies composed of at least three amyloid β peptide subunits, wherein at least one of the amyloid β peptide subunits is an amyloid β peptide analog. The invention further relates to metal complexes of amyloid β peptide assemblies and the use of amyloid β peptide assemblies as vaccines and in the identification of agents that modulate assembly of the amyloid β peptide subunits.
1 . An isolated soluble amyloid β peptide assembly comprising at least three amyloid β peptide subunits, wherein at least one subunit is an amyloid β X-Y peptide analog,
wherein X is an integer between 1 and 28, and Y is 40, 42 or 43; and
wherein when X is 1, the amino acid residue at position 1 is an aspartic acid or a modified amino acid residue.
2 . The assembly of claim 1 , wherein the analog further comprises a label.
3 . The assembly of claim 1 , wherein the analog further comprises one or two additional carboxyl-terminal amino acid residues.
4 . The assembly of claim 1 , wherein the analog comprises the amino acid sequence R 2 -Xaa 1 -Gly-Ala-Ile-Ile-Gly-Leu-Xaa 2 -Val-Xaa 3 -Xaa 4 -Val-Val-R 3 (SEQ ID NO:65),
wherein R 2 denotes a peptide of 0 to 29 amino acid residues in length; Xaa 1 is a basic amino acid residue; Xaa 2 is methionine or a structural derivative thereof; Xaa 3 and Xaa 4 are independently glycine, D-proline or L-proline, with the proviso that both Xaa 3 and Xaa 4 are not simultaneously a proline; and R 3 is a peptide of 0 to 5 amino acid residues in length.
5 . The assembly of claim 1 , further comprising one or more metal atoms.
6 . The assembly of claim 1 , wherein said assembly is produced from a homogenous population of amyloid β peptide subunits.
7 . The assembly of claim 1 , wherein said assembly is produced from a heterogenous population of amyloid β peptide subunits.