Fluorescent Self‐Threaded Peptide Probes for Biological Imaging

A general synthetic method creates a new class of covalently connected, self‐threaded, fluorescent molecular probes with figure‐eight topology, an encapsulated deep‐red fluorophore, and two peripheral peptide loops. The globular molecular shape and rigidified peptide loops enhance imaging performance by promoting water solubility, eliminating probe self‐aggregation, and increasing probe stability. Moreover, the peptide loops determine the affinity and selectivity for targets within complex biological samples such as cell culture, tissue histology slices, or living subjects. For example, a probe with cell‐penetrating peptide loops targets the surface of cell plasma membranes, whereas, a probe with bone‐targeting peptide loops selectively stains the skeleton within a living mouse. The unique combination of bright deep‐red fluorescence, high stability, and predictable peptide‐based targeting is ideal for photon intense fluorescence microscopy and biological imaging.