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Hopkins scientists overcome main obstacle to making tons of short, drug-like proteins

Two Johns Hopkins scientists have figured out a simple way to make millions upon millions of drug-like peptides quickly and efficiently, overcoming a major hurdle to creating and screening huge "libraries" of these super-short proteins for use in drug development.

"Our work dramatically increases the complexity of peptide libraries that can be created and the speed with which they can be made and processed," says Chuck Merryman, Ph.D., a postdoctoral fellow who developed the new technique. "In an afternoon, we'll be able to make literally millions of millions of different peptides with medicinal potential."

Usually less than 40 building blocks long, peptides act as important messengers and hormones in the body. But because their building blocks, called amino acids, are quickly recycled, peptides made from the 20 naturally occurring amino acids don't last long enough to be useful as medicines. However, adding a tiny methyl group to each amino acid gives the resulting peptide "drug-like" stability.

Writing in the April 19 issue of Chemistry & Biology, the Hopkins scientists reveal that using a simple chemical reaction, first reported in the early 1980s, allows them to convert en masse the naturally occurring amino acids to ones that form more stable peptides.

The tricky part, Merryman says, was figuring out how to do the conversion while the amino acids were attached to transfer RNA, a carrier molecule required for the biological production of peptides. The advance makes it possible to build upwards of 10,000,000,000,000 -- that's 1 with 13 zeros behind it -- stabilized, 10-block-long peptides at once.

"The idea of creating large peptide libraries and testing them for medicinal uses has been around a long time, but until now it's just not been very practical," says Merryman.

A key aspect of all scientists' efforts to create libraries of drug-like peptides is "biology in a dish" -- harnessing the same machinery cells use
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Apr-2004


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