Abstract: Disclosed are methods and kits for producing a conformationally constrained peptide, such as a helix constrained peptide, in a cell. In some cases, the methods comprise contacting a cell comprising an intracellularly-localised recombinant peptide with a cross-linker and culturing the cell in the presence of the cross-linker, wherein the cross-linker forms thioether cross-links with at least two derivatisable amino acids located at anchoring positions in the recombinant peptide. The methods and kits and cells find application, for example, in the identification of inhibitors that can be used to disrupt protein-protein interactions.

Abstract: Disclosed are methods, kits and cells for screening an inhibitor of association between candidate binding partners, such as for screening antagonists of amyloid peptides. The methods, kits and cells employ a reporter expression cassette and hybrid proteins. The reporter expression cassette encodes a reporter and comprises at least one DNA binding site. Each hybrid protein comprises a candidate binding partner and a component of a DNA binding protein and, upon association, form a DNA-binding complex capable of binding to the at least one binding site and inhibiting expression of the reporter. The methods, kits and cells find application, for example, in the identification of inhibitors that may be useful in treating diseases associated with protein aggregation, such as Alzheimer's Disease and Parkinson's Disease.

Abstract: Disclosed are methods, kits and cells for screening for test compounds that are capable of inhibiting DNA-binding activity of a DNA-binding protein. The disclosed methods, kits and cells may include a reporter expression cassette that encodes a reporter expression product, wherein the reporter expression cassette comprises at least one binding site for the DNA-binding protein such that binding of the DNA-binding protein to the binding site inhibits expression of the reporter expression product. Also disclosed are methods for producing a helix-constrained peptide that may be used in the screening methods disclosed herein. The methods, kits and cells find application, for example, in the identification of antagonists that may be useful in the treatment of cancers involving the DNA-binding protein.