Molecularly Imprinted Polymeric Receptors with Interfacial Hydrogen Bonds for Peptide Recognition in Water
Milad Zangiabadi, Yan Zhao
Abstract
Protein receptors bind their peptide ligands by a combination of hydrophobic and hydrogen-bonding interactions to achieve high affinity and selectivity. Construction of synthetic receptors for peptides by the same principle, however, is challenging because of the complexity of the guest molecules and subtle structural differences among closely related sequences. Molecular imprinting of peptides in surface–core doubly-cross-linked micelles yielded hydrophobic pockets complementary to the hydrophobic side chains of peptides. Amide-functionalized bis(acrylamide) cross-linkers such as N,N′-methylenebis(acrylamide) (MBAm) used in the core cross-linking installed a layer of hydrogen bonds at the surfactant/water interface and was found to enhance the molecular recognition of peptides in water, particularly hydrophilic ones rich in polar residues. An extremely strong imprinting effect was obtained, with the imprinted/nonimprinted ratio ranging from 3000 to 10000 for model tripeptides. These hydrogen bonds allowed distinction of closely related peptide sequences and enabled a general, simple, one-pot preparation of highly selective receptors for binding complex hydrophilic peptides with <200 nM affinity in aqueous buffer.