Protein properties project aims to guide development of new medicines

Full knowledge of the properties of proteins down to atomic level is essential for making it easier and faster to produce protein-based drugs in liquid form. Over the next four years, a joint European project, PIPPI, co-ordinated by the Technical University of Denmark (DTU), will develop a public database with detailed knowledge of the properties of proteins in pharmaceutical formulations.

With the average age of the European population rising, greater focus is being devoted to manufacturing safe and risk-free drugs, while the requirements for evaluating new drugs and their possible side effects are becoming stricter. Such developments have moved the pharmaceutical industry towards protein-based drugs, which have high specificity and relatively few side effects. But there is very little knowledge about the way these proteins behave in solution.

Together with partners from the pharmaceutical industry (Novozymes, MedImmune, Wyatt Technology); European universities (Manchester; Ludwig-Maximilians Munich, Lunds and Copenhagen) and other stakeholders, DTU has received DKK30m (€4m) from Horizon 2020 towards the development of the database, which aims to ensure more efficient development of the screening process that protein-based drugs, such as next-generation insulins and growth hormones, undergo before being put on the market.

'Drugs as we know them from the pharmacy typically consist of an active substance such as paracetamol in painkillers,' explains Pernille Harris, Associate Professor at DTU Chemistry.

'In addition to the active substance, there are other substances in the finished tablet, for example, excipients facilitating that the tablet is dissolved in the right way and stabilises the active substances.

Initially, a comprehensive protein library will be established, representing the different properties that proteins can have

'Similarly, excipients are added to protein solutions to increase the stability of proteins. Today, the pharmaceutical industry carries out very extensive screening of all these excipients to test their performance with the active substance. It is this screening process that we hope to be able to streamline with this project.'

Novozymes' Senior Scientist Jens Bukrinski says: 'We have high expectations that PIPPI will help boost the knowledge in the field. Furthermore, we hope that PIPPI will result in increased focus to the field, so that Europe can catch up with the US and Asia.'

While paracetamol is a small organic molecule, which will keep for a long time in a tablet, protein-based drugs are more unstable; the challenge in respect of these drugs is, for example, to eliminate the risk of the proteins, in their aqueous solution, precipitating into the solution.

Harris adds: 'Today, the pharmaceutical industry manufactures the drugs by testing and screening until they obtain a solution that keeps the active substance suspended in the liquid. The idea of the project is to establish as many as 15 PhD positions with the various partners in the project at the same time. Initially, a comprehensive protein library will be established, representing the different properties that proteins can have, for example in terms of size, whether they are positively or negatively charged, hydrophobic or flexible. Subsequently, their abilities to interact with various substances will be characterised and everything will be gathered in a database.'

Ultimately, knowledge right down to the atomic level about the different types of proteins may make it easier to predict the behaviour of a similar protein targeted for use by the pharmaceutical industry. The aim is for the protein to be stable in the solution, and although this can be achieved today, getting there may be a long and hard process.

The first PhD positions will be advertised in February 2016.