Compounds that inhibit the interaction between signal-transducing proteins and the glgf (pdz/dhr) domain and uses thereof

A composition capable of inhibiting specific binding between a signal-transducing protein having at its carboxyl terminus the amino acid sequence (S/T)—X—(V/I/L), wherein each — represents a peptide bond, each parenthesis encloses amino acids which are alternatives to one other, each slash within such parentheses separating the alternative amino acids, the X represents any amino acid which is selected from the group comprising the twenty naturally occurring amino acids, and a cytoplasmic protein.

A method of identifying a compound capable of inhibiting specific binding between a signal-transducing protein and a cytoplasmic protein containing the amino acid sequence (G/S/A/E)—L—G—(F/I/L), wherein each — represents a peptide bond, each parenthesis encloses amino acids which are alternatives to one other, each slash within such parentheses separating the alternative amino acids, which comprises:

• (a) contacting the cytoplasmic protein bound to the signal-transducing protein with a plurality of compounds under conditions permitting binding between a known compound previously shown to be able to displace the signal-transducing protein bound to the cytoplasmic protein and the bound cytoplasmic protein to form a complex;
• and
• (b) detecting the displaced signal-transducing protein or the complex formed in step (a), wherein the displacement indicates that the compound is capable of inhibiting specific binding between the signal-transducing protein and the cytoplasmic protein.

A method of identifying a compound capable of inhibiting specific binding between a signal-transducing protein having at its carboxyl terminus the amino acid sequence (S/T)—X—(V/I/L), wherein each — represents a peptide bond, each parenthesis encloses amino acids which are alternatives to one other, each slash within such parentheses separating the alternative amino acids, the X represents any amino acid which is selected from the group comprising the twenty naturally occurring amino acids, and a cytoplasmic protein, which comprises:

• (a) contacting the signal-transducing protein bound to the cytoplasmic protein with a plurality of compounds under conditions permitting binding between a known compound previously shown to be able to displace the cytoplasmic protein bound to the signal-transducing protein and the bound signal-transducing protein to form a complex;
• and
• (b) detecting the displaced cytoplasmic protein or the complex of step (a) wherein the displacement indicates that the compound is capable of inhibiting specific binding between the signal-transducing protein and the cytoplasmic protein.