Probing Peptide Sequences on Their Ability to Generate Affinity Sites in Molecularly Imprinted Polymers

Abstract

An array of 4000 defined and addressable tripeptides on a polymer-coated glass slide is used to synthesize molecularly imprinted polymer (MIP) nanoparticles. This work is undertaken to systematically probe the impact of the peptide sequence on the ability to generate affinity MIPs. The polymer affinity is assessed by measuring the fluorescence of bound MIP nanoparticles at each peptide spot on the surface after washing the array to remove any low-affinity polymer. The generic composition commonly used in the preparation of MIPs against proteins seems to be equally suitable for imprinting hydrophobic and hydrophilic tripeptides. The amino acids frequently contributing to the formation of high-affinity MIPs include T, F, D, N, Y, W, and P. The amino acids that rarely contribute to the formation of high-affinity interactions with MIPs are G, V, A, L, I, and M. These observations are confirmed by computational modeling. The basic technique proposed here may be applicable in optimizing polymer compositions for the production of high-affinity MIPs or, more specifically, for the selection of appropriate amino acid sequences when peptide epitopes are used instead of whole protein imprinting.

Modulation of acetylcholinesterase activity using molecularly imprinted polymer nanoparticles

“…34,35 We have recently patented an experimental approach for using molecular imprinting to identify peptide sequences on the surface of proteins with potential antigenic properties. 36 This method involves the synthesis of MIP NPs in the presence of a whole protein, partial proteolysis of the protein bound to the polymer, and subsequent sequencing of released peptides that were bound to the polymer (Fig. 1).…”

Molecular Dynamics in the Study and Development of Molecularly Imprinted Materials – Status Quo, Quo Vadis?

“…Since force-field based methods are unable to account for electron transfer necessary for bond formation, to date, naturally, most efforts on utilizing MD simulations in MIP development have been focused on modeling solution aspects prior to polymer gelation. Yet, a number of studies have attempted to model the polymerization reaction [189][190][191][192][193][194]. In a paper by Cowen et al [193], a novel algorithm capable of mimicking atomistic radical polymerization of all-component pre-polymerization systems was presented.…”

The Use of Computational Methods for the Development of Molecularly Imprinted Polymers

“…No analysis of the resultant model was reported other than that its density was very similar to that of the polymers prepared by electropolymerization. Cowen and co-workers developed a similar algorithm for simulating the polymerization reaction during MD simulations of the pre-polymerization mixture [ 502 , 503 ]. Briefly, after equilibration of the system, new bonds were formed between “reactive” atoms within a suitable distance followed by another round of energy minimization.…”