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Breakthrough for more efficient drug development
Date:1/18/2011

Developing new drugs is a highly costly and time-consuming process. Of 20 candidates, 19 are normally rejected because they don't work or have unwanted side effects. Now a research team led by Professor Lars Baltzer at Uppsala University has produced a tiny molecular "binder" that has the potential to change this landscape radically.

The study, published today in the prestigious journal Angewandte Chemie, presents the concept of a tiny polypeptide consisting of 42 amino acids to which virtually any target-seeking organic molecule can be bound. In the body it then seeks out the designated sites to be treated. What's unique about the polypeptide is that it dramatically enhances the properties of the little molecule in a simple and very general way.

- This produces superbinders. They bind more strongly and more specifically than other alternatives, says Lars Baltzer, professor of organic chemistry, who believes it will be possible to rapidly develop new drugs much more readily with this new concept.

The whole concept goes against the grain of what is usually done in drug development. Traditionally it's usually a matter of synthesizing drugs from A to Z, with certain requirements needing to be met in order to succeed. Drugs should be low molecular (500 Da), be highly fat soluble, and have no more than ten binding sites in order to pass through the cell membrane. But the majority are ineffective or toxic, and nowadays there are also ways to get larger molecules through cell membranes. Recently therapeutic antibodies have emerged as an alternative. They're large (150,000 Da) and bind to the outside of cells, which they then "block."

The new peptide is 5,000 Da or only 1/30 as large as a typical antibody, which is smaller than was thought possible. But according to Lars Baltzer nature has always signaled that this should work.

- The human growth factor hGH uses 35 amino acids to bind to its receptor, but
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Contact: Lars Baltzer
lars.baltzer@biorg.uu.se
46-070-648-2595
Uppsala University
Source:Eurekalert

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