Method for predicting protein aggregation and designing aggregation inhibitors

A method for producing a protein aggregation inhibiting peptide, including the steps of:

• a) identifying a peptide sequence forming at least part of an aggregation region in a target protein;
• b) testing whether said peptide sequence forms part of a β-sheet;
• c) if a positive result is achieved in step b), extracting the adjacent strands of that sheet;
• d) identifying residues in the adjacent strands to said peptide sequence whose side chains interact with said peptide sequence, those residues forming a potential protein aggregation inhibiting peptide sequence,
• e) synthesising a peptide library, the members of said peptide library comprising the residues identified in step d), and
• f) determining the affinity of the members of said library for the target protein.

A method of designing compounds to be used to inhibit the activity of a target peptide or polypeptide, including the steps of:

• a) identifying a peptide sequence forming at least part of an active region in a target protein;
• b) testing whether said peptide sequence forms part of a β-sheet;
• c) if a positive result is achieved in step b), extracting the adjacent strands of that sheet;
• d) identifying residues in the adjacent strands to said peptide sequence whose side chains interact with said peptide sequence, those residues forming a potential protein aggregation inhibiting peptide sequence;
• and
• e) using the residue(s) identified in step d) of to design compounds which will inhibit the activity of the target protein.