Thursday, January 26, 2012

Twenty-year protein mystery solved with surprising results

In spite of more than 20 years of research efforts, the enzymatic function of the CRYM protein has remained elusive. Previous research has shown that CRYM functions both as an important structural protein and a binder of thyroid hormones, but PhD student Andre Hallen suspected something more.

"CRYM was first discovered in the ocular lens of marsupials, that is, in Skippy's eye! Since then, we've seen it in lamb brains, in other tissues and learnt how it can be observed and mutated in mammals like humans. Now we can see more of its full potential in human health and nutrition," Hallen explains.

In a study published in the , Hallen conclusively demonstrated an for CRYM, and identified how this reveals a new role for in regulating mammalian amino acid metabolism.

It also recognises a possible reciprocal role of enzyme activity in regulating bioavailability of intracellular T3, with further research pathways for how this regulatory role might open up new treatment options for a range of neurological and .

Hallen lead a team of scientists on this study, including three months working in North America with Dr Arthur Cooper, a world authority on neurochemistry and amino acid chemistry.

His research has also sparked the interest of , including Patrick W Reed and Robert J Bloch of the University of Maryland, who profiled Hallen's work in their article ‘Crystallin-Gazing: Unveiling Enzymatic Activity'.

In 2012, Hallen will continue his research into this area, further exploring the role of diet in influencing hormone function, and the effects of these changes on the CRYM protein, its related mutations and conditions.

Provided by Macquarie University

Algae for your fuel tank: New process for producing biodiesel from microalgae oil

Plant oils from sources such as soybean and rapeseed are promising starting materials for the production of biofuels. Microalgae are an interesting alternative to these conventional oil-containing crops. Microalgae are individual cells or short chains of cells from algae freely moving through water. They occur in nearly any pool of water and can readily be cultivated. "They have a number of advantages over oil-containing agricultural products," explains Lercher. "They grow significantly faster than land-based biomass, have a high triglyceride content, and, unlike the terrestrial cultivation of oilseed plants, their use for does not compete with food production."

Previously known methods for refining oil from microalgae suffer from various disadvantages. The resulting fuel either has too high an and poor flow at low temperatures, or a sulfur-containing catalyst may contaminate the product. However, other catalysts are still not efficient enough. The Munich scientists now propose a new process, for which they have developed a novel catalyst: nickel on a porous support made of zeolite HBeta. They have used this to achieve the conversion of raw, untreated algae oil under mild conditions (260 °C, 40 bar hydrogen pressure). Says Lercher: "The products are diesel-range saturated hydrocarbons that are suitable for use as high-grade fuels for vehicles."

The oil produced by the is mainly composed of neutral lipids, such as mono-, di-, and triglycerides with unsaturated C18 fatty acids as the primary component (88 %). After an eight-hour reaction, the researchers obtain 78 % liquid alkanes with octadecane (C18) as the primary component. The main gas-phase side products are propane and methane.

Analysis of the reaction mechanism shows that this is a cascade reaction. First the double bonds of the unsaturated fatty acid chains of the triglycerides are saturated by hydrogen. Then, the now saturated fatty acids take up hydrogen and are split from their glycerin component, which reacts to form propane. In the final step, the acid groups in the fatty acids are reduced stepwise to the corresponding alkane.

More information: Towards Quantitative Conversion of Microalgae Oil to Diesel-Range Alkanes with Bifunctional Catalysts, B. Peng, Y. Yao, C. Zhao und J.A. Lercher, Angewandte Chemie, 2011. doi:10.1002/ange.201106243

Provided by Technische Universitaet Muenchen

New chemical reaction holds promise for drug development

The team -- led by Brian Stoltz, the Ethel Wilson Bowles and Robert Bowles Professor of Chemistry, and Doug Behenna, a scientific researcher -- used a suite of specialized robotic tools in the Caltech Center for Catalysis and to find the optimal conditions and an appropriate catalyst to drive this particular type of reaction, known as an alkylation, because it adds an alkyl group (a group of carbon and ) to the compound. The researchers describe the reaction in a recent advance online publication of a paper in Nature Chemistry.

"We think it's going to be a highly enabling reaction, not only for preparing complex natural products, but also for making pharmaceutical substances that include components that were previously very challenging to make," Stoltz says. "This has suddenly made them quite easy to make, and it should allow medicinal chemists to access levels of complexity they couldn't previously access."

The reaction creates called heterocycles, which involve cyclic groups of carbon and . Such nitrogen-containing heterocycles are found in many and pharmaceuticals, as well as in many . In addition, the reaction manages to form carbon-carbon bonds at sites where some of the are essentially hidden, or blocked, by larger nearby components.

"Making carbon-carbon bonds is hard, but that's what we need to make the complicated structures we're after," Stoltz says. "We're taking that up another notch by making carbon-carbon bonds in really challenging scenarios. We're making carbon centers that have four other carbon groups around them, and that's very hard to do."

The vast majority of pharmaceuticals being made today do not include such congested carbon centers, Stoltz says—not so much because they would not be effective compounds, but because they have been so difficult to make. "But now," he says, "we've made it very easy to make those very hindered centers, even in compounds that contain nitrogen. And that should give pharmaceutical companies new possibilities that they previously couldn't consider."

Perhaps the most important feature of the reaction is that it yields almost 100 percent of just one version of its product. This is significant because many exist in two distinct versions, or enantiomers, each having the same chemical formula and bond structure as the other, but with functional groups in opposite positions in space, making them mirror images of each other. One version can be thought of as right-handed, the other as left-handed.

The problem is that there is often a lock-and-key interaction between our bodies and the compounds that act upon them—only one of the two possible hands of a compound can "shake hands" and fit appropriately. In fact, one version will often have a beneficial effect on the body while the other will have a completely different and sometimes detrimental effect. Therefore, it is important to be able to selectively produce the compound with the desired handedness. For this reason, the FDA has increasingly required that the molecules in a particular drug be present in just one form.

"So not only are we making tricky carbon-carbon bonds, we're also making them such that the resulting products have a particular, desired handedness," Stoltz says. "This was the culmination of six years of work. There was essentially no way to make these compounds before, so to all of a sudden be able to do it and with perfect selectivity… that's pretty awesome."

More information: "Enantioselective construction of quaternary N-heterocycles by palladium-catalysed decarboxylative allylic alkylation of lactams," Nature Chemistry.

Provided by California Institute of Technology (news : web)

Researchers seek high-pressure materials without high-pressure processes

The Defense Advanced Research Projects Agency's (DARPA's) Extended Solids program seeks to identify processes that enable stabilization and production of high pressure phase , without the limitations of scale introduced by current high-pressure processes, that exhibit properties far superior to those currently available for DoD applications.

"We seek the ability to access these ultrahigh pressure phases without having to use the ultrahigh pressures currently required to achieve them," said Judah Goldwasser, DARPA's program manager for this effort. "In the thermochemical world, the ability to synthesize the vast array of materials available both biochemically and synthetically is predicated on exploitation of multistep synthesis and stabilization strategies, so target materials can be produced through intermediates using methods and conditions mild enough to be viable."

Through this program, DARPA seeks the development of analogous strategies that can be applied to the barochemistry, or ultrahigh pressure regime. This technology could fundamentally change the way high-pressure polymorphs/phases are synthesized, potentially opening a vast new material design space for exploitation.

Goldwasser stressed that the complex nature of this research effort requires diverse sets of skills and expertise to meet program objectives and milestones, and encouraged potential researchers to team with others to help ensure success.

Provided by Defense Advanced Research Projects Agency