Interferons are proteins produced by the human body which can be used to treat various diseases. For example, interferon beta is one of the few substances which can be used to treat multiple sclerosis. But the low solubility of the protein poses a major problem. Scientists at the Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB are now attempting to replace the hydrophobic (water-repelling) portions of the molecule by soluble ones. The technique is known as hydrophobicity engineering. The goal is to reduce clustering between the molecules in order to increase the protein yield and thus pharmacological effectiveness. The variant molecules are constructed by means of genetic engineering methods: they are produced in bacteria cells, then all traces of bacterial protein is removed until ultra-pure interferon beta remains.

The researchers' first step was to determine a structural model for human interferon beta. They based this on the three-dimensional crystalline structure of mouse interferon beta – the make-up of the proteins is very similar in the two species. "By means of homology-based modelling we were then able to reproduce the model of the human interferon beta protein", reports Christian Schneider-Fresenius of the IGB. "We had to take that course because when we started work nobody knew the crystalline structure of human interferon beta." In the meantime scientists in the USA have determined its structure; a comparison with the model revealed the same underlying structure. Then the IGB researchers had to identify the amino acids responsible for low solubility, in order to replace them with more soluble ones. This improved the basic biophysical properties of the protein, without affecting its biological activity.

The work of the IGB has shown that designing large intact proteins requires very precise knowledge of the relationships between structure and function and also the physico-chemical interactions taking place in a protein. In the process, the scientists were pioneering a possible way for future pharmaceutical research: natural proteins are indispensable for developing highly specific drugs to fight diseases which we have not yet conquered. However, it will be some time before tailor-made proteins with deliberately altered properties can be used on patients.