Design and synthesis of artificial receptors for phosphorylated amino acids.

The research detailed in this thesis describes the development of a high-throughput molecularly imprinted polymer (MIP) receptor that binds to phosphorylated serine residues. This new receptor would need to be biologically compatible (i.e. binds in aqueous media) and have a high degree of specificity and affinity for the phosphorylated residue compared to the non-phosphorylated amino acid. Importantly, the artificial receptor should not rely on neighbouring amino acid residues for its binding affinity or specificity. Different molecular imprinting approaches were investigated to imprint the template molecule, Boc-phospho-L-serine methyl ester. The most successful approach was found by using an amidine group in stoichiometric monomer-template interactions. To determine the binding affinity and specificity of the MIP, an equilibrium evaluation was used. Batch analyses for the template specie and a range of cross-reactants were performed in aqueous systems and the enantioselectivity was evaluated using the D-enantiomer of the template molecule. Furthermore, the selectivity of the MIP was investigated with a series of peptides containing phosphorylated serine. The results of these studies provide evidence of selective binding sites in the MIP for Boc-phospho-L-serine methyl ester. The thesis concludes by discussing some applications of the MIP in life sciences, e.g. as an alternative to antibody assays