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

Hydrated lipid structures, such as liposomes, that display tethered metal-i on-chelating groups have proven useful in peptide and protein binding, as w ell as 2D protein crystallization through molecular recognition of accessib le histidine sites in proteins and peptides. Polymerizable metal-ion-chelat ing 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 lipi d that can be used in the fluid, i.e., liquid analogous, phase of lipid bil ayers. The synthesis of 1-palmitoyl-2-[8- [(E,E)-2',4'-hexadienoyloxy] octa noyl] -sn-glycero-3-N-[11 -[N',N'-bis [carboxymethyl]imino] -3,6,9-trioxaun decanoyl] phosphatidylethanolamine (1) is described. The chelator moiety, i minodiacetate (IDA), was linked to the polymerizable phosphatidylethanolami ne (PE) with a terminal 2,4-hexadienoyl (sorbyl) group through an oligo(eth ylene glycol)-based spacer. Lipid l-Cu complex is designed to be combined w ith the corresponding polymerizable matrix lipids (bis-SorbPC) to form func tionalized liposomes that can be stabilized by various polymerization metho ds.