RESULTS MAY INSPIRE NEW TREATMENTS FOR LEAD POISONING

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RESULTS MAY INSPIRE NEW TREATMENTS FOR LEAD POISONING
02 May 2007 - DOE/Brookhaven National Laboratory

Scientists from the U.S. Department of Energy’s Brookhaven National Laboratory and the University of Chicago have discovered that a member of a well-known protein family is better at detecting lead than any other known substance. Learning more about the protein’s structure and lead-detection mechanism, they say, may lead to new ways to synthesize drugs or to develop treatments for lead poisoning, a worldwide problem that, in the U.S. alone, inflicts irreversible physical damage to half a million children each year.

In fact, the results, online version of Angewandte Chemie International Edition, show that the protein is more than one thousand times more likely to bind to lead than other metals, such as mercury, zinc, or copper.

To determine this, the researchers used a method developed by one of the paper’s co-authors, University of Chicago chemist Chuan He. They bind the protein to a short segment of double-stranded DNA that will fluoresce (emit light) if the DNA strands are separated. With no lead nearby, the two strands of the DNA double helix stay “zipped,” and there is no fluorescence. But when a common lead ion, known as lead(II), binds to the protein, the DNA strands “unzip,” releasing a burst of ultraviolet light.

The scientists tested the protein’s response to the presence of several metals. Most elicited little to no reaction from the protein, producing fluorescence barely above the constant background level. The lead(II) ion, however, induced a large jump in the fluorescence intensity, three times brighter than background.

“This fluorescence method converted the protein into an excellent lead(II)-ion probe,” said He. “It has the potential to be used for rapid, on-the-spot lead detection in many situations, such as in homes.”

Van der Lelie, He, and their collaborators plan to further study the structure of the protein, which may reveal why the molecule is so selectively “interested” in lead ions. This information could be used to design lead-poisoning treatment agents that would bind only to lead ions in the body. Current treatments are not so selective, also stripping away beneficial metals, such as iron and zinc, which results in serious side effects.

The scientists will also attempt to optimize the DNA-probe method so that the probe emits visible light. This would simplify detection and increase the probe’s practicality. The group will also apply similar strategies to developing sensor systems for other metal ions.

http://www.bnl.gov

About: DOE/Brookhaven National Laboratory
Established in 1947 on Long Island, Upton, New York, Brookhaven is a multi-program national laboratory operated by Brookhaven Science Associates for the US Department of Energy (DOE). Six Nobel Prizes have been awarded for discoveries made at the Lab.

Brookhaven has a staff of approximately 3,000 scientists, engineers, technicians and support staff and over 4,000 guest researchers annually.

Brookhaven National Laboratory's role for the DOE is to produce excellent science and advanced technology with the cooperation, support, and appropriate involvement of our scientific and local communities. The fundamental elements of the Laboratory's role in support of the four DOE strategic missions are the following:

To conceive, design, construct, and operate complex, leading edge, user-oriented facilities in response to the needs of the DOE and the international community of users.

To carry out basic and applied research in long-term, high-risk programs at the frontier of science.

To develop advanced technologies that address national needs and to transfer them to other organizations and to the commercial sector.

To disseminate technical knowledge, to educate new generations of scientists and engineers, to maintain technical capabilities in the nation's workforce, and to encourage scientific awareness in the general public.

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