METHODS AND COMPOSITIONS FOR MODULATING THE Wnt PATHWAY

An isolated cyclic peptide comprising the amino acid sequence:

• X0X1X2X3, where X0 is N;
• X1 is F, Y, L, A, R, or S;
• X2 is I or V;
• and X3 is K, R, or H.

An isolated peptide comprising the amino acid sequence:

• X−1 X0X1X2, where X−−1 is W, L, Y, F, or I;
• X0 is D or E;
• X1 is F, W, I, S, or Y;
• and X2 is M.

A method for screening for a compound that inhibits the interaction of Dkk1 and LRP6 comprising

• contacting a test compound with LRP6, or functional equivalent thereof, and
• determining the level of binding of the test compound to the LRP6, or functional equivalent thereof, in the presence and the absence of a peptide ligand that inhibits the interaction of Dkk1 with LRP6,
• wherein a change in level of binding in the presence or absence of the peptide ligand indicates that the test compound inhibits the interaction of Dkk1 with LRP6,
• and wherein the peptide ligand comprises an amino acid sequence selected from the group consisting of the amino acid sequences of
• a) Family 1 (FIG. 1);
• b) Family 2 (FIG. 2);
• c) Family 3 (FIG. 3);
• and
• d) Family 4 (FIG. 4).

A method for screening for a compound that inhibits the interaction of Dkk1 and LRP5 comprising

• contacting a test compound with LRP5, or functional equivalent thereof, and
• determining the level of binding of the test compound to the LRP5, or functional equivalent thereof, in the presence and the absence of a peptide ligand that inhibits the interaction of Dkk1 with LRP5,
• wherein a change in level of binding in the presence or absence of the peptide ligand indicates that the test compound inhibits the interaction of Dkk1 with LRP5
• and wherein the peptide ligand comprises an amino acid sequence selected from the group consisting of the amino acid sequences of
• a) Family 1 (FIG. 1);
• b) Family 2 (FIG. 2);
• c) Family 3 (FIG. 3);
• and
• d) Family 4 (FIG. 4).