Molecular imprinting for protein recognition: Current status, challenges and applications

Abstract

Molecular recognition plays a critical role in numerous living systems. Over the past several decades, considerable attempts have been made to create synthetic recognition systems with high specifity and selectivity for a certain molecue by utilizing natural receptors such as antibodies, receptors, enzymes and aptamers. Despite their high selectivity and broad range of applications, these biomolecules always suffer from some drawbacks, for example, instablity in harsh condition, high production cost. In response to these limitations, the alternative molecular imprinting technique has attracted a number of researchers sustain interests, shows a promising potential in the creation of synthetic recognition systems. Molecular imprinting, a synthetic Lock to Key technique that uses molecular templates to create selective binding sites in cross-linked polymers, has become one of the most efficient methods for preparation of selective recognition materials. To date, a wide range sizes of template including inorganic ions, drugs, nucleic acids, peptides, proteins, viruses, and whole cells have been extensively applied in the synthesis of various specific molecularly imprinted polymers. Among them, the majority of the publications and successful applications in molecular imprinting are aimed at recognition and separation of small molecules. Molecular imprinting of biomacromolecules, especially proteins, still remains great challenges. Due to its large size, environmentally instability, chemical and structural complexity, traditional imprinting methods were limited and not suitable for proteins. Since 2011, protein imprinting has acheived some significant breakthroughs in imprinting methods and applications. On one hand, some novel and special protein imprinting methods have been developed, such as nanomaterial-based imprinting, boronate affinity-based surface imprinting, epitope imprinting, solid-phase synthesis and post-imprinting modification. These newly emerging methods effectively solved some key issues in protein imprinting and were applied for synthesis of MIPs with special properties that were not well demonstrated before. In this paper, we have analyzed the merits and problems of these methods in detail. On the other hand, based on the novel protein imprinting materials with special properties, some new advanced applications, such as disease diagnosis, proteomics and bioimaging, have well been demonstrated and showed great potentials. In addition, the future challenges and opportunities in protein imprinting were also discussed. Despite the tremendous interest in protein imprinting, related research studies were still behind compared to the progress made in molecular imprinting of small molecules. Particularly, the design of universal protein imprinting materials with desirabe properties still remains great challenges. As to future development, developing facile and versatile protein imprinting methods is still of significant importance. Meanwhile, as a multidisciplinary technology, protein imprinting should develop rapidly along with the advances in polymer technology, nanotechnology, analytical chemistry, biotechnology and so on. We forsee that, in a long period of time, creating new protein imprinting strategies, developing desirable protein imprinting materials with special properties based on borrowing and integration of related technologies/strategies, and thereby enable potential important applications are still the main direction of protein imprinting.