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Light activated 'warhead' turns modest molecules into super protein killers
Date:3/14/2010

JUPITER, FL, March 10, 2010 Using a novel light activation technique, Scripps Research Institute scientists have been able to turn molecules with only a modest ability to fight specific proteins into virtual protein destroyers.

The new technique, which uses a "warhead" molecule capable of inactivating nearby proteins when triggered by light, could help to accelerate the development of new therapies by providing researchers with a new set of research tools and options.

The study was published March 14, 2010 in an advanced, online edition of the journal Nature Chemical Biology.

"High-throughput screening can produce a synthetic ligand [peptoid] capable of binding to just about any protein you want," said Thomas Kodadek, a professor in the Department of Chemistry at the Institute's Jupiter, Florida, campus, who led the study. "The problem is, they almost always have modest potency which makes them less than ideal research tools. By attaching this 'warhead' molecule to a peptoid, we've shown that we can increase that protein-killing potency by a thousand fold without going through an expensive and time-consuming optimization process."

The new technique offers researchers rapid access to some very potent, very selective light activated compounds that can knock out specific protein function, an important strategy in research into diseases such as cancer. Since light can be focused with high spatial resolution, this technology may open the door for knocking out proteins in only one region of a single cell, but not another, allowing, for example, the inactivation of a target protein in the nucleus, but not in the cytoplasm that surrounds it.

A Choice of Warheads

The technique is known as a CALI, which stands for chromophore-assisted light inactivation; chromophores are molecules that can absorb visible or ultraviolet light. While other researchers have made CALI reagents previously, they suffered from p
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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