title: Challenges for the effective molecular imprinting of proteins.
abstract: Molecular imprinting is a technique that is used to create artificial receptors by the formation of a polymer network around a template molecule. This technique has proven to be particularly effective for molecules with low molecular weight (<1500 Da), and during the past five years the number of research articles on the imprinting of larger (bio)templates is increasing considerably. However, expanding the methodology toward imprinted materials for selective recognition of proteins, DNA, viruses and bacteria appears to be extremely challenging. This paper presents a critical analysis of data presented by several authors and our own experiments, showing that the molecular imprinting of proteins still faces some fundamental challenges. The main topics of concern are proper monomer selection, washing method/template removal, quantification of the rebinding and reproducibility. Use of charged monomers can lead to strong electrostatic interactions between monomers and template but also to undesired high aspecific binding. Up till now, it has not been convincingly shown that electrostatic interactions lead to better imprinting results. The combination of a detergent (SDS) and AcOH, commonly used for template removal, can lead to experimental artifacts, and should ideally be avoided. In many cases template rebinding is unreliably quantified, results are not evaluated critically and lack statistical analysis. Therefore, it can be argued that presently, in numerous publications the scientific evidence of molecular imprinting of proteins is not convincing.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.
authors.forename: Ellen
authors.initials: E
authors.lastname: Verheyen
authors.forename: Joris P
authors.initials: JP
authors.lastname: Schillemans
authors.forename: Martin
authors.initials: M
authors.lastname: van Wijk
authors.forename: Marie-Astrid
authors.initials: MA
authors.lastname: Demeniex
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
mesh_terms: D054802:Molecular Imprinting / Q000379:methods*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
chemical_list: D011108:Polymers; D011506:Proteins