Small molecules for imaging protein-protein interactions

Abstract

A tissue is imaged to detect the presence of amyloid deposits or other target proteins prior to their aggregation into plaques, with the assistance of the administration of a labeled bifunctional compound of which one functionality binds to the target protein and the second functionality binds to a chaperone protein that is present in the tissue of interest. The two functionalities have different binding affinities, the target-binding functionality having the greater binding affinity, with the result that the bifunctional compound preferentially remains in the tissue when bound to the chaperone and then the target protein while bifunctional compound that is not bound to the target protein will leave the tissue. The inclusion of the chaperone allows the imaging process to detect the non-aggregated proteins by way of the label and the difference in kinetics of the binding to the chaperone and the target protein permits one to distinguish between binding of the bifunctional molecule to the chaperone only and binding to the chaperone and then to the target protein. Certain intermediates toward the synthesis of these bifunctional compounds are novel by themselves, and labeled bifunctional molecules in general that utilize a lysine linker are also disclosed as a novel class of compounds.