HER-2-SPECIFIC CYCLIZED SUPR PEPTIDES
Disclosed are highly potent peptides, peptide conjugates, host cells and compositions containing one or more of these peptides, peptide conjugates and/or host cells that are useful to inhibit the growth of a breast cancer cell or treat breast cancer in a patient in need of such treatment.
1 . A Scanning Unnatural Protease Resistant (SUPR) peptide comprising a non-naturally occurring amino acid sequence of MVCVVLYDDK.
2 . The peptide of claim 1 , wherein the M at position 1 is substituted with norvaline, norleucine, or alanine.
3 . The peptide of claim 1 , wherein the Vat position 2 is substituted with I or L.
4 . The peptide of claim 1 , wherein the V at position 4 is substituted with Y, F, P, D, E, or M.
5 . The peptide of claim 1 , wherein the V at position 5 is substituted with Y, F, D, E, W, C, G, or P.
6 . The peptide of claim 1 , wherein the L at position 6 is substituted with Y, F, V, V, I, P, or C.
7 . The peptide of claim 1 , wherein the Y at position 7 is substituted with V, E, or D.
8 . The peptide of claim 1 , wherein the D at position 8 is substituted with S, T, E, Y, F, A, P, or V.
9 . The peptide of claim 1 , wherein the D at position 9 is substituted with E, G, L, I, or V.
10 . The peptide of claim 1 , wherein the K at position 10 is substituted with lysine derivatives e.g. Orn.
11 . A peptide, having the structure:
12 . A peptide, having the structure:
13 . A peptide, having the structure:
14 . A peptide, having the structure:
15 . A peptide, having the structure:
16 . A peptide, having the structure:
17 . A peptide, having the structure:
18 . A peptide, having the structure:
19 . A peptide, having the structure:
20 . A peptide, having the structure:
21 . A peptide, having the structure:
22 . A peptide, having the structure:
23 . A peptide, having the structure:
24 . A peptide, having the structure:
25 . A peptide, having the structure:
26 . A peptide, having the structure:
27 . A peptide, having the structure:
28 . The peptide of claim 1 , comprising a label.
29 . The peptide of claim 28 , wherein the label is a dye.
30 . The peptide of claim 29 , wherein the dye is Cy5.
31 . The peptide of claim 28 , wherein the label is an in vivo imaging agent.
32 . The peptide of claim 31 , wherein the in vivo imaging agent is 18F.
33 . The peptide of claim 1 , wherein the label is a cytotoxin or radioactive atom such as 90Y that can be used for therapeutic applications.
34 . The peptide of claim 1 , further comprising a pharmaceutically acceptable carrier.
35 . A method for inhibiting the growth of an HER-2+ breast cancer cell, comprising contacting the cell with a therapeutically effective amount of the peptide of claim 1 .
36 . A method for treating HER-2+ breast cancer in subject in need thereof, comprising administering to the subject the therapeutically effective amount of the peptide of claim 1 .
37 . A method imaging a HER-2+ cell in a subject, comprising administering to the subject the HER-2-specific cyclized SUPR peptide of claim 28 in an amount sufficient to image the cell.
38 . A kit for one or more of: inhibiting the growth of a HER-2+ breast cancer cell, for treating a HER-2+ breast cancer, or for imaging a HER-2+ cancer in a subject, comprising the peptide of claim 1 and instructions for use.
39 . The kit of claim 38 , further comprising a label.