Phosphatidylethanolamine (PE) is a major constituent of cellular membranes and plays critical roles in membrane dynamics, signalling, and apoptosis.1,2 Despite its biological importance, selective molecular tools for the recognition and visualisation of PE remain limited. Here, we report the design and characterisation of a fluorescent peptide-based sensor for the selective detection of PE. The probe incorporates an environment-sensitive nitrobenzoxadiazole (NBD) fluorophore, a dipicolylamine (DPA) receptor unit, and a crown ether motif as a secondary recognition element. In the presence of Zn²⁺, the DPA moiety forms a metal complex that enables recognition of the anionic phosphate headgroup of PE, while the crown ether provides additional stabilising interactions with the ethanolamine moiety.
Binding interactions between the probe and PE were investigated using model liposome systems and NMR titration experiments. Fluorescence studies revealed an enhancement in emission intensity upon binding to PE-containing liposomes, demonstrating high sensitivity and selectivity over other phospholipids. NMR titration experiments further confirmed the formation of a stable probe–PE complex and provided insight into the binding mode.
Together, these results establish this dual-receptor peptide as an effective fluorescent sensor for PE. This work provides a versatile platform for the development of PE-targeted probes and offers new opportunities for studying PE-associated biological processes in membrane systems.