Conformationally dynamic peptides
Disclosed are novel peptides that are useful, for example, for detecting target proteins having a β-sheet secondary structure which may be associated with a disease, and for diagnosing and treating such a disease. Related methods and kits also are disclosed.
1. A peptide probe for Aβ protein, wherein the peptide probe is a peptide or peptide mimic that comprises an amino acid sequence that
(i) is a variant of SEQ ID NO: 1 that differs from SEQ ID NO: 1 by one or more amino acid substitutions selected from G29H, G29R, G29K, and G33E that introduces a salt bridge into the peptide probe sequence wherein G29H, G29R and G29K correspond to residue 14 of SEQ ID NO:1 and G33E corresponds to residue 18 of SEQ ID NO:1; or
(ii) comprises the amino acid sequence selected from SEQ ID NOs: 2-4, 14-17, 19-21, 23-24, 28-35, 38-43, 49-50 and 52, having a salt bridge in the peptide probe sequence.
2. The peptide probe of claim 1 , wherein the peptide probe is labeled with a detectable label.
3. The peptide probe of claim 2 , wherein the peptide probe is labeled with two or more labels.
4. The peptide probe of claim 3 , wherein the peptide probe is labeled with a detectable label pair selected from an excimer pair, a FRET pair and a fluorophore/quencher pair.
5. The peptide probe of claim of claim 1 , wherein the amino acid sequence of the peptide probe is a variant of SEQ ID NO: 1 that differs from SEQ ID NO: 1 by one or more substitutions selected from the group consisting of G29H, G29R, G29K, and G33E.
6. The peptide probe of claim 1 , wherein the amino acid sequence of the peptide probe comprises the amino acid sequence selected from the group consisting of SEQ ID NOs: 2-4, 14-17, 19-21, 23-24, 28-35, 38-43, 49-50 and 52.
7. The peptide probe of claim 1 , wherein the amino acid sequence of the peptide probe comprises the amino acid sequence of SEQ ID NO: 2 (Peptide 22).
8. The peptide probe of claim 1 , wherein the peptide probe is conjugated to a soluble polyethylene glycol moiety.
9. The peptide probe of claim 2 , wherein the detectable label is conjugated at a site selected from the group consisting of (i) a side chain of a terminal lysine residue; (ii) a side chain of an internal lysine residue.
10. The peptide probe of claim 1 , wherein the peptide probe is conjugated to a biotin moiety directly or through a peptide linker.
11. The peptide probe of claim 10 , wherein the linker comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 56-60.
12. The peptide probe of claim 10 , wherein the peptide probe is conjugated to a biotin moiety through a side chain of an internal lysine residue.