Molecular Recognition Enhanced by Multifunctional Affinity Ligands: Applications to Biomolecule Binding and Targeting
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Hydrated lipid structures, such as liposomes, that display tethered metal ion-chelating groups have proven useful in peptide and protein binding, as well as 2-D 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 prepared. The chelator moiety, iminodiacetate (IDA), was linked to the polymerizable phosphatidylethanolamine (PE) with a terminal 2,4-hexadienoyl (sorbyl) group through an oligoethylene glycol-based spacer. The Lipid-chelate-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. Two-dimensional imprinting of biological molecules on a liposome surface has been accomplished by use of polymerizable functional lipids and matrix lipids. The imprinted liposomes should show higher and more specific binding of template molecules, which are important for many biological applications including liposome targeting, (drug delivery, imaging), bioseparations, biosensors, etc. In this work we present preliminary work of design and synthesis of a new polymerized, multifunctional (multiple) chelating-liposomes in which the chelator lipids were imprinted by myoglobin surface histidines. Some evidence of imprinting and selective binding is shown by comparison of competitive binding between myoglobin and other proteins to the template polymerized liposomes and random polymerized liposomes.