Abstract: A new procedure for creating macromolecular receptors for peptides using molecular imprinting has been developed. The polymeric receptor exhibits selective uptake of specific N- terminal histidine containing sequences of simple dipeptides. The polymerization and binding are carried out in water. The approach utilizes a strong Ni(II)-His binding to attract the N- terminus histidine of the dipeptide to the polymer surface and secondary interactions between peptide and polymer to discriminate between the peptide sequence. These developments are enabled by utilizing an aqueous based monomer formulation that includes N,N'-ethylenebis(acrylamide) as a water-soluble cross-linking monomer and a polymerizable NTA ligand, which can be used to incorporate nickel and other metals into these polyacrylamides. The Ni-NTA complex provides a strong histidine binding site that draws the dipeptide to the polymer surface. Mild polymerization conditions that utilize low concentrations of water-soluble initiator and low-temperature result in quantitative polymer yields. Variation of monomer composition reveals an optimum cross-linking for achieving maximum selectivity for these polymers

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