Synthesis of a polymerizable metal-ion-chelating lipid for fluid bilayers

Hydrated lipid structures, such as liposomes, that display tethered metal-ion-chelating groups have proven useful in peptide and protein binding, as well as 2D protein crystallization through molecular recognition of accessible histidine sites in proteins and peptides. Polymerizable metal-ion-chelating lipids bearing a reactive diacetylene group have been described. These interesting compounds can be polymerized in the solid-analogous phase. Here we describe the design of the first polymerizable metal-ion-chelating lipid that can be used in the fluid, i.e., liquid analogous, phase of lipid bilayers. The synthesis of 1-palmitoyl-2-[8-[(E,E)-2',4'-hexadienoyloxy]octanoyl]-sn-glycero-3-N-[11-[N',N'-bis[carboxymethyl]imino]-3,6,9-trioxaundecanoyl] phosphatidylethanolamine (1) is described. The chelator moiety, iminodiacetate (IDA), was linked to the polymerizable phosphatidylethanolamine (PE) with a terminal 2,4-hexadienoyl (sorbyl) group through an oligo(ethylene glycol)-based spacer. Lipid 1-Cu complex is designed to be combined with the corresponding polymerizable matrix lipids (bis-SorbPC) to form functionalized liposomes that can be stabilized by various polymerization methods.