NOVEL METHODS FOR PREPARING SYNTHETIC ANTIBODIES

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This proposal aims to continue the work on the fabrication of robust, selective, chemical receptors for proteins using polymerized liposomes. During this project period, the method will be developed to a high degree of selectivity. After the optimization studies, the liposomes will be tested for separation of proteins, biological imaging, targeted delivery and the fabrication of biosensors. The proposed method for creating stable chemical receptors for proteins relies on creating a three dimensional pattern of metal ions, ion pairs and hydrogen bonding sites on a liposome, complementary to the pattern exhibited by the protein of choice. Mixed polymerizable liposomes will be prepared with ionic lipids, lipids (quaternary ammonium salts), metal-chelating lipids and lipids with primary amine moiety on their head-groups. Polymerizable diacyl phosphocholine (zwitter ionic) will be used as the major constituent of these liposomes. After fabrication, these liposomes (in the unpolymerized state) will be allowed to interact with the selected protein. Due to the lateral diffusional mobility of the lipids, the metal ions on the liposome surface will orient complementary to the pattern of surface-exposed histidines of the protein. The quaternary ammonium headgroups on the liposomes will be positioned by the acidic amino acid side chains (Asp, Glu) on the protein surface. Amino acid side chains of the protein capable of forming hydrogen bonds (e.g., Ser, Thr, Lys, Asn, Gln and Arg) will interact with the primary amine moieties on the liposome. The result of this equilbration step is the creation of a pattern of metal ions, charges and hydrogen bonding sites on the liposome surface complementary to the surface pattern exhibited by the protein. These patterned liposomes will then be photo-polymerized to capture and lock the surface pattern created by the equilibration step. The polymerized liposomes will "recognize" the selected protein by a wide array of simultaneous and complementary interactions in three dimensions; hence binding between the liposomes and the protein will be strong and selective.