Funding: ANR-18-CE19-023-02
January 2019- June 2022

The concept of ‘molecular imprinting’ emerged in the 1930’s and thanks to its conceptual simplicity, it always attracted a tremendous interest of many scientific communities. The goal is to obtain the hollow shape of a molecule (i.e. ‘template ‘) in a three-dimensional matrix. The template is then removed from the material to give the empty cavities, which are now able to selectively capture the initial object (i.e. the template molecule). These molecular imprints were obtained either inside a material (e.g. hydrogel, macroporous matrix etc.) or on the surface of a substrate. Both organic or inorganic polymerization of monomeric precursors have been used to prepare imprinted materials. However, most of precursors (monomers) commonly used for molecular imprinting are organic ones that react between them by free radical polymerization.

In this sense, the objective of Peptimprint is to set-up a ground-breaking technology to prepare highly specific tridimensional and functionalized imprints of biomolecules (peptides, proteins) by template-assembly, but in this case following the inorganic polymerization by sol-gel process. For that, a variety of original hybrid building blocks mimicking amino acids (diketopiperazine) will be synthetised and developed to be used as precursors (functional monomers) in the MIP synthesis. Unfunctionalized blocks (e.g. tetraethoxysilane (TEOS), methyltriethoxysilane, dimethyldiethoxysilane, bis(triethoxysilyl) ethylene, mono-silylated PEG or bis-silylated PEG) will be also used concomitantly to create the network. Once the template molecule removed, the hollow cavities will be able to capture the biomolecule which was previously imprinted with very high selectivity and affinity. Indeed, unlike classical molecular imprint polymers (MIPs), the resulting inorganic/bioorganic hybrid material will recapitulate not only the shape but also the complementary functions of the biomolecular template.

This project is developed in collaboration with team “Analytic Sciences of Biomolecules & Molecular Modelling” of the Institute of Biomolecules Max Mousseron (IBMM), the team “Molecular Chemistry and Solid-state Organization (CMOS)” of the Institute Charles Gerhardt (ICG), the team “Optomicrofluidique (POMM)” from the Charles Coulomb laboratory of the University of Montpellier, and the team interactions of the “Institut de Recherche en Cancérologie de Montpellier” (IRCM).


Gilles Subra
Ahmad Mehdi
Pascal Verdier
Pierre Martineau
Martine Pugniere
Giang NGO

Development of Amino Acids Functionalized SBA-15 for the Improvement of Protein Adsorption

Molecules 202126(19), 6085;


Ordered mesoporous materials and their modification with multiple functional groups are of wide scientific interest for many applications involving interaction with biological systems and biomolecules (e.g., catalysis, separation, sensor design, nano-science or drug delivery). In particular, the immobilization of enzymes onto solid supports is highly attractive for industry and synthetic chemistry, as it allows the development of stable and cheap biocatalysts. In this context, we developed novel silylated amino acid derivatives (Si-AA-NH2) that have been immobilized onto SBA-15 materials in biocompatible conditions avoiding the use of toxic catalyst, solvents or reagents. The resulting amino acid-functionalized materials (SBA-15@AA) were characterized by XRD, TGA, EA, Zeta potential, nitrogen sorption and FT-IR. Differences of the physical properties (e.g., charges) were observed while the structural ones remained unchanged. The adsorption of the enzyme lysozyme (Lyz) onto the resulting functionalized SBA-15@AA materials was evaluated at different pHs. The presence of different functional groups compared with bare SBA-15 showed better adsorption results, for example, 79.6 nmol of Lyz adsorbed per m2 of SBA-15@Tyr compared with the 44.9 nmol/m2 of the bare SBA-15.

Sol-gel process – the inorganic approach in protein imprinting

J. Mater. Chem. B, 2021 Jan.


Proteins play a central role for the signal transmission in living systems since they are able to recognize specific biomolecules acting as cellular receptors, antibodies or enzymes; or being themselves recognized by other proteins in protein/protein interactions, or displaying epitopes suitable for antibody binding. In this context, the specific recognition of a given protein, unlocks a range of interesting applications in diagnosis and in targeted therapies. Obviously, this role is already fulfilled with antibodies with unquestionable success. However, the design of synthetic artificial systems able to endorse this role is still challenging with a special interest to overcome limitations of antibodies, in particular their production and their stability. Molecular Imprinted Polymers (MIPs) are attractive recognition systems which could be an alternative for the specific capture of proteins in complex biological fluids. MIPs can be considered as biomimetic receptors or antibodies mimics displaying artificial paratopes. However, MIPs of proteins remains a challenge due to their large size and conformational flexibility, their complex chemical nature with multiple recognition sites and their low solubility in most organic solvents. Classical MIP synthesis conditions result in large polymeric cavities with and unspecific binding sites on the surface. In this review, the potentiality of sol-gel process as inorganic polymerization strategy to overcome the drawbacks of protein imprinting is highlighted. Thanks to the mild and biocompatible experimental conditions required and the use of water as solvent, the inorganic polymerization approach suits better to proteins than organic polymerization. Through numerous examples and applications of MIPs, we proposed a critical evaluation of the parameters that must be carefully controlled to achieve sol-gel protein imprinting (SGPI), including the choice of the monomers taking part in the polymerization.

Date Congress Type presentation Title presentation
15-18 June 2021 Balard Chemistry Conferences 2021 Oral Communication Biomimetic protein imprinting on magnetic particles using amino acid-based hybrid blocks
18 June 2021 aesap (Association des Enseignants de Sciences Analytiques de Pharmacie Flash Communication Silylated amino acids as hybrid precursors for protein-biomimetic surface coating: application to electrophoresis separation
22-24 June 2021 Affinity 2021 Flash Communication Amino acid-based hybrid blocks for biomimetic protein imprinting
5-7 July 2021 ISOS-2021 The 19th International Symposium on Silicon Chemistry Flash Communication
14 July 2021 e-MSB 2021 Boston Oral Communication Silylated amino acids as hybrid precursors for protein-biomimetic surface coating: application to electrophoresis separation
5-7 October 2021 SEP21- 14ème Congrès Francophone sur les Sciences Séparatives et les Couplages de l’AFSEP Oral communication Silylated amino acids as hybrid precursors for protein-biomimetic surface coating: application to electrophoresis separation


28-29 October 2021 JMJC2021 9èmes Journées Méditerranéennes des Jeunes Chercheur(e)s Poster Communication Applications of silylated amino acid in the development of hybrid materials
Oral Communication Silylated amino acids as hybrid precursors for molecularly
imprinted polymers
2-3 November 2021 QSense User Days – Biolin Scientific Oral Communication Using QCM-D to study the recognition of molecularly imprinted polymer particles toward their target proteins