Synergistic Multiple Weak Interactions Enable Precise Recognition of Glycoproteins via Molecular Imprinting

Protein molecular imprinting is an important research direction for protein recognition and is expected to become a powerful tool for disease diagnosis and treatment. However, molecularly printed polymers (MIPs) primarily rely on single-action recognition and respond poorly to the complex conformations of proteins, resulting in suboptimal selectivity. Inspired by the multivalent synergistic weak interaction in biomolecular recognition, based on the recognition strategy of biomimetic multiple weak interactions, ovalbumin (OVA) was used as an example target template, four functional monomers were used as raw materials to provide multiple binding sites related to the hydrogen bonding, electrostatic interaction, hydrophobic interaction, and π-π stacking, and MIPs with multiple biomimetic molecular interactions were prepared. By surface imprinting, high-performance MIPs were successfully prepared. The adsorption capacity of MIP on OVA was as high as 84 mg/g, the binding rate was fast, and the imprinting factor was IF = 1.49. The relationship between molecular selectivity and MIP polymerization time was studied, and the necessity of MIP for four functional monomers was confirmed; the MIP performance of protein was related to a variety of weak interactions. Molecular simulations revealed the synergistic enhancement mechanism of the MIP selectivity by multiple monomers. This MIP can recognize OVA proteins with a high selectivity from the egg complex matrix. The new biomimetic imprinting method with multiple interactions established in this study is expected to be an efficient protein recognition strategy.