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Chemical library aids in developing drug system for nerve damage

A researcher studying drug design for nerve damage therapies has gotten her answer to questions by following some old advice: she used the library.

It's not the kind of library her mother or teacher suggested, but a combinatorial chemistry library of many different protein sequences that some day might help her and her colleagues develop a successful timed drug delivery system.

Shelly Sakiyama-Elbert, Ph.D., assistant professor of biomedical engineering at Washington University in St. Louis, has screened a large number of molecules to find which ones have varying affinity, or attraction, to a sugar that binds nerve repair drugs called heparin, as well as a nerve repair protein called nerve growth factor.

Sakiyama-Elbert ran a library of viruses called bacteriophages that contained small random portions, or sequences of their surface proteins which could be used to attract or bind other proteins through a column with the drug bound to it. She then made the playing field more difficult for the bacteriophage to bind so that eventually she could find bacteriophage peptides that bound to heparin or nerve growth factor. By repeating this process numerous times, she identified peptide sequences that have low, medium or high affinity for the heparin drug.

Sakiyama-Elbert and her colleagues are looking for protein sequences that bind to drugs to help a drug delivery vehicle provide timed release of a drug. Such drug delivery systems are called affinity-based, and it is hoped that eventually they will provide the signals necessary to stimulate tissue regeneration for conditions such as nerve damage on an appropriate time scale.

In conjunction with the sequence technique, Sakiyama-Elbert and her group developed a mathematical model that identifies the kind of drug release desired as a basis to narrow down the range of affinities they want to identify from the library. Between the modeling and future ex
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Contact: Tony Fitzpatrick
tony_fitzpatrick@wustl.edu
314-935-5272
Washington University in St. Louis
12-Apr-2005


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