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

oor efficiency, largely due to self-inactivation. The new warhead used by the Scripps Florida team represents a significant advance.

They used a derivative of ruthenium, a metallic element that produces what is known as singlet oxygen, the well known oxygen molecule, O2.

"When the ruthenium absorbs visible light," Kodadek said, "it has to dump that energy to return to a normal state. In the process, it produces an extremely reactive form of oxygen that rips apart whatever proteins it happens to encounter. Basically, it destroys those proteins forever."

While there have been reports of other "warhead"-carrying peptoids, the study said, the ruthenium derivative used by Kodadek and his colleagues is an important technical advance, one that allows scientists to target both extracellular and intracellular protein targets. Unlike organic singlet oxygen generators, the Ru complex is itself insensitive to singlet oxygen, greatly increasing the efficiency of CALI.

The other important point, the study noted, is that these new peptoids have no effect on any cellular components until they are activated by light.

Simple synthetic compounds like peptoids have many advantages over other ligands molecules that bind to proteins and alter their function such as antibodies, Kodadek pointed out. They can be modified easily for attachment to surfaces and can be produced relatively quickly in large amounts a multi-million member peptoid library, for example, can be created in about three days.

This makes them ideal building tools for biomedical research, the study said.

Kodadek became interested in developing this new technique when he and Benjamin Cravatt, chair of the Scripps Research Department of Chemical Physiology, decided to combine separate technologies a peptoid library synthesis and screening platform developed in the Kodadek laboratory in Florida and activity-based protein profiling (ABPP) developed in Cra
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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