Protein Surface Recognition with Targeted Fluorescent Molecular Probes

Protein surface recognition by fluorescent molecular sensors poses an immense challenge in supramolecular recognition chemistry owing to the immense difficulty of selectively targeting these large, relatively flat and non-contiguous domains. The fact that protein surfaces can exhibit different charges, topologies, and posttranslational modifications that can be found in other proteins in the mixture is an additional factor that complicates targeting and therefore, sensing specific protein surface modifications. A recent report, however, shows that the difficulty of sensing changes that occur on the surface of specific proteins could be circumvented by attaching a relatively non-specific synthetic receptor to a specific protein binder. The latter brings the receptor near the target protein and enhances its affinity toward its surface. Modifying the synthetic receptor with an environmentally sensitive fluorescent reporter along with suitable recognition elements enables such systems to target specific regions on protein surfaces and consequently, track modifications that result from conformational changes or binding interactions.