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New high-throughput screening technique makes probing puzzling proteins possible
Date:3/29/2009

Understanding the tens of thousands of proteins that compose the human proteome has emerged as a key challenge of this century, and research efforts to date have already enabled major advances in drug discovery and understanding basic biology. But many potential avenues have been blocked by lack of information about how the majority of these proteins function.

The bulk of these so far enigmatic proteins may now be open to study, thanks to research by a team at The Scripps Research Institute and its Molecular Screening Center.

The scientists have developed the first widely applicable high-throughput screening technique that works even with proteins about which little is known, enabling searches for the molecules these proteins interact with, and for inhibitors that might block, the proteins' activity. Already, the new technique, described in the March 29, 2009 edition of the journal Nature Biotechnology, has allowed the team to identify inhibitors for two enzymes thought to play significant roles in cancer progression.

Most studies of enzymes rely on substrate assays, which allow researchers to visibly track the enzymes' activity. Working with substrates is critical to better understand both basic cellular functioning and to identify molecules that inhibit the activity of enzymes that play critical roles in diseases such as cancer, advancing potential drug treatments.

One major hurdle in protein research, though, is that developing conventional substrate assays and related tools demands knowledge of the molecules with which a given protein binds. But such information is available for only about a third of the proteome.

"The remaining two thirds or so of these proteins are to a large extent totally uncharacterized," says Ben Cravatt, chair of the Department of Chemical Physiology at Scripps Research and corresponding author of the new study, "and that presents major challenges."

To nudge proteomic
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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