Beta-catenin targeting peptides and uses thereof
AssigneePresident and Fellows of Harvard College
InventorsGregory L. Verdine, Tom N. Grossmann, Tsung-Han Johannes Yeh
Life of this patent
Estimating the term…
Abstract
The invention relates to β-catenin targeting peptides comprising an a-helical segment that are optionally stapled or stitched, and pharmaceutical compositions thereof. Uses of the inventive β-catenin targeting polypeptides including methods for treatment of disease, such as diseases associated with aberrant Wnt signaling, including cancer, are also provided.
Claims26
An isolated polypeptide comprising an α-helical segment, wherein the peptide binds β-catenin.
-12. (canceled)
-16. (canceled)
A β-catenin binding polypeptide comprising an α-helical segment, wherein the polypeptide comprises the amino acid sequence:
- X1X2X3X4X5Y1X6X7X8Y2X9X10X11X12X13X14X15,
- wherein
- X1 is selected from the group consisting of R, K and no amino acid;
- X2 is selected from the group consisting of R, K, W and no amino acid;
- X3 is selected from the group consisting of W, Y and Q;
- X4 is selected from the group consisting of P, S, W, A, F and L;
- X5 is selected from the group consisting of E, Q, R and W;
- X6 is selected from the group consisting of I and L;
- X7 is selected from the group consisting of I and L;
- X8 is selected from the group consisting of D and N;
- X9 is selected from the group consisting of H and W;
- X10 is selected from the group consisting of V, W, L, M, F, and I;
- X11 is selected from the group consisting of Q, E, L, D, H, R, S, and V;
- X12 is selected from the group consisting of R, S, and K;
- X13 is selected from the group consisting of V, I, L, W, F and H;
- X14 is selected from the group consisting of M, Norleucine, I, L, W, F and H;
- X15 is selected from the group consisting of R, G, P, E, H, K, Q, and no amino acid;
- and
- Y1 is selected from the group S, S5, R5, and Y2 is selected from the group E, S5, and R5.
A β-catenin binding polypeptide comprising an α-helical segment, wherein the polypeptide comprises the amino acid sequence:
- X1X2X3X4X5X6X7X8X9X10X11X12X13X14X15X16,
- wherein
- X1 is selected from the group consisting of R, V, E, Q, T, K, W, and L;
- X2 is selected from the group consisting of W, S, L, N, Y, K, V, and Q:
- X3 is selected from the group consisting of P, L, S, W, A, and F;
- X4 is selected from the group consisting of E, Q, and W;
- X5 is S;
- X6 is I;
- X7 is L;
- X8 is D;
- X9 is selected from the group consisting of E and Q;
- X10 is H;
- X11 is selected from the group consisting of W, V, F, M, L, and I;
- X12 is selected from the group consisting of E, Q, H, D, V, and L;
- X13 is selected from the group consisting of R and K;
- X14 is selected from the group consisting of V and W;
- X15 is selected from the group consisting of M, W, F, and E;
- and
- X16 is selected from the group consisting of R, G, P, E, and Q, with the proviso that the sequence is not the wild-type sequence from Axin, ENPESILDEHVQRVMR (SEQ ID NO:
- 1) (amino acids 469-484 of rat axin) or ENPESILDEHVQRVLR (SEQ ID NO:
- 2) (amino acids 465-480 of human axin).
A β-catenin binding polypeptide comprising an amino acid sequence of any one of the sequences set forth in FIG. 6b.
-47. (canceled)
(canceled)
(canceled)
(canceled)
Dependencies are inferred from the claim text.