Artificial insulin receptors from molecularly imprinted polymer nanoparticles

The treatment of chronic diseases requires highly effective drugs with minimal side effects. The peptide hormone insulin plays a key role in the treatment of diabetes. Since the number of diabetes mellitus diseases is constantly increasing, increasingly larger quantities of insulin must also be produced. Nowadays, insulin is produced on an industrial scale using recombinant microorganisms. In order to be able to use the protein molecules as active ingredients, they have to be purified in a multi-stage process that is both time-consuming and costly. Up to 50 per cent of the production costs of protein therapeutics arise during the purification process. With the help of effective artificial adsorbers or receptors that reversibly bind insulin, the purification process could be considerably simplified and thus become more economical.

Objective: Specific insulin receptors

At the Institute of Interfacial Engineering (IGVT) at the University of Stuttgart we are investigating the representation of molecularly imprinted nanoparticles (MIPs, molecular imprinted polymers), which could bind insulin with high specificity and selectivity. The work is part of the "New materials from bionics" programme of the Landesstiftung Baden-Württemberg foundation.

Principle of molecular imprinting

Principle of molecular imprinting.
Figure 1: The principle of molecular imprinting.

Molecular imprinting is a process in which a polymerizable mixture with non-polymerizable target molecules - here insulin - is converted into nanoscopically small polymer beads. During polymerization, the insulin molecules act like molecular stamps, so-called templates, and leave specific imprints for the peptide in the plastic surface of the resulting beads. Once the template is removed, specific insulin recognition sites are released in the nanostructured polymers - artificial receptor nanoparticles would be created (Figure 1).

Challenge binding points

3D-structure of insulin.
Figure 2: 3D-structure of insulin. The peptide sequence of the N-terminus of the B-chain utilized for imprinting has been highlighted.

What sounds visionary is basically feasible with the method used at the IGVT. A particular challenge in the realisation of artificial receptor nanoparticles for recombinant human insulin is the design of the binding sites. Using computer-assisted evolutionary methods, we select those peptide sequences from the insulin molecule that appear to be particularly suitable for a successful imprinting process: They should be specific for insulin and be spatially easily accessible in the insulin molecule. MIPs imprinted with a specific peptide sequence should thus be able to recognise the entire insulin molecule. So far, we have defined three such sequences. One of them, consisting of six amino acids, is shown in Figure 2 together with the insulin molecule.

Outlook

There may still be a long way to go before the artificial receptors can be used for purification during insulin production. The current high cost of insulin purification and the urgent need for insulin - in 2007 the insulin market generated a global turnover of US $ 5 billion - is a lasting motivation for our research.

Promotion

The project "Biomimetic insulin adsorber material based on evolutionarily developed molecularly imprinted nanoparticles" is funded by the Landesstiftung Baden-Württemberg foundation as part of the "New materials from bionics" programme.

Project partners

In addition to the experimental work at the IGVT, the Institute of Industrial Science and Technology Management (IAT) at the University of Stuttgart analyses and evaluates patent and regulatory conditions for artificial adsorber materials in purification processes.