23 September 2009

Wrap the protein preparation in a polypeptide

One of the main methods of treating hepatitis B is injections of drugs containing interferon. But interferon is a relatively small protein that is very quickly excreted from the body through the kidneys, and patients have to inject large doses of the drug every other day. However, interferon remains in the bloodstream much longer if its molecules are bound to molecules of polyethylene glycol – a spiral polymer that is able to absorb water, increasing in volume. As a result, the polyethylene glycol molecule becomes too large to pass through the kidney filtration system, and the bound interferon remains in the circulatory system much longer. Due to this, injections are enough to do once every 1-2 weeks. The disadvantage of the method is the accumulation of a harmless, but foreign substance in the body.

Professor Arne Skerra of the Technical University of Munich (TUM) and the staff of the Biochemistry Department of the Weihenstephan Center (Chair of Biological Chemistry at the Center for Life and Food Sciences Weihenstephan) synthesized polypeptide molecules from three alternating amino acids: proline, alanine and serine (PAS). These molecules, like polyethylene glycol, increase their volume in the presence of water, but they are quickly destroyed and excreted from the body. Interferon, which, like any protein, also consists of amino acids, can be enclosed in a shell of PAS molecules. In the first animal tests, scientists found out that the half-life of "rasilized" interferon in the blood is much higher than usual, which means a significant increase in the intervals between injections.

With the help of PAS technology, it is possible to prolong the action of any protein preparations – for example, growth factors or functional fragments of antibodies (in the figure above, such a fragment is a red and black globule wrapped in a gray PAS shell). In addition, genes encoding both PAS and therapeutic protein can be inserted into the chromosomes of genetically modified bacteria and ready-made medicinal substances can be obtained in one stage, which will significantly reduce the cost of production. The realization of this idea is the next stage of the scientists' work.

Professor Skerra and his colleagues have created a new biotech company – XL-protein GmbH – and are confident that with the help of their technology it is possible to create a new generation of drugs – potential blockbusters. Several of the new drugs are already in the late stages of preclinical studies.

Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert: Researchers prolong the plasma half-life of biopharmaceutical proteins


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