Synchrotron & Neutron Users’ Group (SNUG) DC Visit, March 2007

Improved Catalysts Reduce COImproved Catalysts Reduce CO22 Emissions Emissions

Acrylonitrile-based acrylic fibers are used to make many things, for example clothing, carpeting, blankets and rubber for hoses and gaskets.

About 5,000,000 tons of acrylonitrile are made each year, with CO2 as an undesirable byproduct. Neutron powder diffraction analyses have been critical to the development of manufacturing catalysts that perform best at the high reaction temperatures,

therefore reducing COreducing CO22 by as much as 33% by as much as 33%

compared to previous catalysts.

Work funded by Innovene

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Synchrotron & Neutron Users’ Group (SNUG) DC Visit, March 2007

New Organic Conductor for Electronic DevicesNew Organic Conductor for Electronic Devices

Research team includes Merck Chemicals (UK), Palo Alto Research Center (California), Stanford University, and SSRL

McCulloch et al., Nature Materials, March 2006.Science (311), March 2006.

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Crystal Power. New semiconducting plastics form large crystals that help whisk electrical charges at higher speeds than ever before.

Scientists have developed a new organic polymer that can be laid down using simple printing techniquessimple printing techniques rather than the expensive and elaborate methods used to process silicon, 6 times faster6 times faster than previous organic

polymers. Now just as fast as silicon plus much cheaper, this inexpensive organic conductor could be used in areas where silicon struggles to compete, eventually slashing the cost of transistors, PDA’s, flat panel screens and bringing electronic paper into common use.

Synchrotron & Neutron Users’ Group (SNUG) DC Visit, March 2007

Nobel Prize Work on Gene TranscriptionNobel Prize Work on Gene Transcription

Research team includes Stanford University, SSRL, and LBNL

Wang, D., Bushnell, D.A., Westover, K.D., Kaplan, C.D., and Kornberg, R.D. (2006) Structural basis of transcription: role of the trigger loop in substrate specificity and catalysis. Cell 127,

941.

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Cutaway view of the Pol II transcribing complex. Template DNA, nontemplate DNA, RNA, GTP in the A site, are shown in cyan, green, red, orange, respectively. The bridge helix (Rpb1 815- 848) is in green; trigger loop (Rpb1 1065-1110) is in magenta and Mg2+ ions are shown in magenta spheres. The pol II surface is shown in gray.

Life as we know it depends on turning on and off the proper genes at the correct time. Gene transcription is how our DNA gets translated into proteins, and ultimately into biological organisms. This work done by the 2006 Chemistry Nobel Prize Laureate Roger Kornberg at the SSRL and ALS synchrotrons shows the structural basis of this. This work can potentially lead to insights into cancer treatment, gene therapy, and other important disease treatments.

This process of gene expression starts when an RNA message is copied from DNA. But the exact mechanism by which RNA does this has not been well understood. The study revealed that a structural element of the RNA enzyme

called the trigger loop is involved.

Synchrotron & Neutron Users’ Group (SNUG) DC Visit, March 2007

In Alzheimer’s Disease (AD), the brain contains a buildup of a misfolded protein, called “plaque,” that is believed to kill brain cells. It is thought that normal metal ions in the brain play a role in plaque formation. At the NSLS and APS, scientists showed that copper and zinc ions accumulate in AD plaques, suggesting that metal ions may impact plaque formation.

These findings can be used for developing drugs developing drugs to preventto prevent this process.

Funded by National Institutes of Health

Eli Lilly is in the process of starting a collaboration to extend this work

L. Miller et al., J. Structural Biology in press.

Preventing Plaque FormationPreventing Plaque Formationin Alzheimer’s Diseasein Alzheimer’s Disease

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Synchrotron & Neutron Users’ Group (SNUG) DC Visit, March 2007

Slowing the Progress of AIDSSlowing the Progress of AIDS

AIDS caused by HIV virus, which produces 12 different kinds of proteins. Organic compounds that interact with these proteins, interfere with virus reproduction are potential drugs for treatment of AIDS.

V. Stoll, et al., Bioorg. Med. Chem. 2002, 10, 2803-2806.

• X-ray crystallographic studies at IMCA-CAT of protein HIV protease reveal atomic details of how compounds interact with protein.

• Also: determination at IMCA of crystallographic structure of the Abbott Laboratories pharmaceutical known as Kaletra®.

• Since FDA approval in 2000, Kaletra® has had positive impact on progression of the AIDS in patients infected with HIV virus.

•In 2002, Kaletra® became most-prescribed (“preferred”) drug in its class for AIDS therapy; referred to as a drug that helped turn a situation where patients were dying from AIDS to a situation where patients are living with AIDS.

Important weapon in battling the scourge of HIVhas been forged from knowledge gained at the APS

Close-up view of the drug binding site within HIV protease. A mathematically calculated surface (orange) shows the active site of the protein is a cavity inside the protein. The drug fits inside this cavity, much like a key fits into a lock. X-ray crystallography studies provided the scientific details of how the atoms of Kaletra® (carbon atoms are gray; nitrogens, blue; oxygens, red) interact with the viral protein.

Abbott Laboratories

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