Antibodies recognize antigens with spectacular selectivities employing a large number of weak complementary interactions extending over a wide surface area. The present proposal aims to mimic this recognition with rationally designed, robust systems of much less complexity. To simplify receptor design, strong directed metal-to-ligand interactions will be used in conjunction with weak ion-pair interactions in an antibody mimic. This interaction is much stronger than hydrogen bonding, ion-pair and Van der Waal's interactions. Hence, fewer number of individual interactions between the target and receptor are required to achieve strong and selective binding. A wide variety of transition metal ions and ligands are available - thus it is possible to fine-tune the strength and kinetics of each interaction. The metal ion depending on its oxidation state, can have a range of spectroscopic properties which can be judiciously used to gain structure information about the receptor-target complex. Polymerizable mixed liposomes will be prepared from transition metal containing, charged and neutral lipids. These liposomes, above the gel-transition temperature, will be allowed to interact with a protein of choice. Due to fluxionality of the lipid bilayer, the metal ion containing lipids will be positioned complementary to the pattern of surface-exposed histidines on one side of the protein; charged head groups of the lipids will interact with the charged residues on the protein surface, close to the histidines. The result is the creation of a pattern of metal ions and charges on the liposome surface complementary to the pattern exhibited by the protein. Liposomes will now be cooled down and photopolymerized in presence of the protein template to lock this surface arrangement of metal ions and charges. The polymerized liposome will now recognize the protein template by a wide array of complementary functionalities. This method is very general and powerful yet simple to construct receptors for proteins. Resultant """"""""synthetic antibodies"""""""" will have wide-ranging applications in affinity separation of proteins, diagnostic imaging, targeted drug delivery, directed agglutination and in construction of novel, robust biosensors.
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