Disheveled pdz modulators

An isolated polypeptide that binds specifically to Dvl PDZ at a binding affinity of IC50=1.5 uM or better.

An isolated polypeptide that binds specifically to Dvl PDZ and comprises a carboxyl terminal region comprising an amino acid sequence selected from the group consisting of the sequences of Table 1 and FIG. 1A for positions −5 to 0, or positions −6 to 0, wherein amino acid numbering is based on the C-terminus residue being in position 0.

A method of rationally designing a modulator of Dvl PDZ-ligand interaction comprising designing the modulator to comprise or mimic the function of a C-terminal peptide comprising a sequence with Gly at position −2, Trp or Tyr at position −1, Phe or Leu at position 0, and a hydrophobic or aromatic residue at position −3, wherein amino acid numbering is based on the C-terminus residue being in position 0, wherein the modulator is capable of specifically binding to Dvl PDZ.

A method of screening for an agent that modulates Dvl PDZ-ligand interaction, wherein the method comprises the steps of:

• (a) providing a candidate agent, contacting said agent with a reaction mixture comprising Dvl PDZ and a known binding parter of said Dvl PDZ, wherein said mixture is a cell mixture or a cell-free mixture, and the contacting occurs under conditions suitable for Dvl PDZ-binding partner interaction;
• (b) determining amount of Dvl PDZ-binding partner interaction in the presence and absence of the agent;
• whereby a difference between the amount of interaction as determined in (b) in the presence and absence of the agent indicates that the agent is a modulator of Dvl PDZ-ligand interaction.