Molecularly imprinted polymers: Synthetic antibody mimics for diagnostics and therapy

30.11.2022 von 09:30 bis 11:00

Kaiserstr. 2, 24143 Kiel, D-Aquarium

Molecularly imprinted polymers (MIPs)1 are synthetic antibody mimics that specifically recognize molecular targets. They are highly cross-linked polymers synthesized in the presence of the target molecule or an 'epitope' thereof, acting as a molecular template. This templating induces three-dimensional binding sites in the polymer that are complementary to the template in size, shape and chemical functionality (Figure 1). The synthetic antibody can recognize and bind its target with an affinity and selectivity similar to a biological antibody.

Herein, we demonstrate the potential of MIP nanogels (size below 100 nm) as antibody mimics directed against peptide epitopes of target proteins, for diagnostics, bioimaging and therapy, on the example of cell surface targets (cadherins - cell-cell adhesion proteins),2,3 as well as a soluble biomarker for kidney injury (KIM1).4 The MIP is obtained through a rational approach using in silico epitope identification followed by solid-phase synthesis of polymer nanogels around the immobilized template peptide. Affinity and specificity are assessed through equilibrium binding assays and solution STD and WaterLOGSY NMR spectroscopies, before the MIPs are tested in bioassays.

 

 

Figure I

 

 

 

 

 

 

Figure 1: General principle of molecular imprinting : Functional monomers interact with the target antigen (molecular template), followed by cross-linking polymerization, resulting in the formation of specific binding cavities in the 3D polymer network.

 

References

[1] Haupt, K., Medina Rangel, P.X., Tse Sum Bui, B. (2020) Molecularly Imprinted Polymers: Antibody mimics for bioimaging and therapy. Chem. Rev. 120, 9554-9582.

[2] Medina Rangel, P.X., Moroni, E., Merlier, F., Gheber, L.A., Vago, R., Tse Sum Bui, B., Haupt, K. (2020) Chemical antibody mimics inhibit cadherin-mediated cell-cell adhesion: A promising strategy for cancer therapy. Angew. Chem. Int. Ed. 59, 2816-2822

[3] Medina Rangel, P.X.,  Mier, A., Moroni, E., Merlier, F., Gheber, L.A., Vago, R., Maffucci, I., Tse Sum Bui, B., Haupt, K. (2022) Molecularly imprinted polymer nanogels targeting the HAV motif in cadherins inhibit cell-cell adhesion and migration. J. Mater. Chem. B  10, 6688-6697.

[4] Mier, A., Maffucci, I., Merlier, F., Prost, E., Montagna, V., Ruiz-Esparza, G.U., Bonventre, J.V., Dhal, P.K., Tse Sum Bui, B., Sakhaii, P., Haupt K.(2021) Molecularly Imprinted Polymer Nanogels for Protein Recognition: Direct Proof of Specific Binding Sites by Solution STD and WaterLOGSY NMR Spectroscopies Angew. Chem. Int. Ed. 60, 20849-20857.

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