Thursday, March 17, 2011

Chemist discovers shortcut for processing drugs

A prolific University of Missouri chemist has discovered a quicker and easier method for pharmaceutical companies to make certain drugs.


Jerry Atwood, Curator's Professor and Chair of the Department of in the MU College of Arts and Science, has recently published a paper – his 663rd in a refereed journal – that states that highly pressurized carbon dioxide at room temperature could replace the time consuming and expensive methods currently used to manufacture certain pharmaceutical drugs.


In the article, "A New Strategy of Transforming Pharmaceutical Crystal Forms," published in a recent edition of the (JACS), Atwood and a team of researchers explain how manufacturers of popular drugs such as clarithromycin (an antibiotic drug) and lansoprazole (an acid reflux drug) could benefit from this process.


To develop basic drugs that are safe for people to consume, manufacturers must utilize chemistry to make specific crystals that constitute the eventual compound. Depending on the drug, current methods may include high-temperature heating, raw material altering, washing, filtering, and intensive drying. Atwood's team found that pressurizing carbon dioxide can bring about the desired crystallization "with ease" and at normal room temperatures. Atwood said this discovery has the potential to streamline work flow and provide more safety for those who work with these chemicals.


"I believe this could have huge implications for the pharmaceutical industry," Atwood said. "In addition to streamlining processes, pressurizing gas could circumvent some of the more difficult techniques used on an industrial scale, leading to better pharmaceuticals, more effective treatments and ultimately a lower price."


Atwood points out that cost savings may be minimal to consumers, however, as drug companies set prices to recoup billion dollar investments in multiple-drug trials. Only one of every five clinically tested drugs makes it to market, Atwood said, and the companies must make a profit on the drug that becomes widely used.


The JACS paper was recognized by Chemical & Engineering News in its "News of the Week," an accomplishment Atwood has achieved nine times. Despite all of his success, Atwood remains focused on his ultimate goal: to develop a chemotherapy with a magnetic component that could bring targeted delivery of medication, rather than the bloodstream saturation process used now.


"When I lecture a group of world-class scientists, I tell them the good news and the bad news," Atwood said. "The bad news is that we must make a major breakthrough like curing a disease. If we can do that, then our field of chemistry will flourish, and we will pay society back for their investment. If we fail to make the breakthrough, society won't support what we are doing forever. The good news is that just one of our research groups has to do it, so the pressure is on all or us, not just on you or me."


Provided by University of Missouri-Columbia (news : web)

Cell component involved in triggering cat allergy

A breakthrough by scientists at The University of Nottingham could provide hope for any allergy sufferers who have ever had to choose between their health and their household pet.


The team of immunologists led by Drs Ghaem-Maghami and Martinez-Pomares in the University’s School of Molecular Medical Sciences, and funded by the charity UK, have identified a cell component which plays a key role in triggering allergic responses to cat dander.


The discovery furthers our understanding of how the body’s identifies and reacts to allergens, which could pave the way in developing new ways of treating allergies.


The development is especially good news for the millions of people with asthma whose condition is often worsened by their allergy to airborne allergens from cat dander or house dust mite. Cat dander consists of microscopic pieces of cat skin which easily become airborne.


Dr. Amir Ghaem-Maghami said: “There has been a sharp increase in the prevalence of allergies over the past few decades and allergic asthma among children has reached epidemic proportions in many industrialised countries, including the UK.


“Despite improvements in patient care, three people die every day in the UK from asthma, and most therapies target symptoms rather than curing the condition.


“Many people with asthma are highly sensitive to airborne allergens such as cat dander or house dust mite — in fact many studies have shown that up to 40 per cent of children with asthma are allergic to cat allergens.


“A better understanding of how the interaction between allergens and the immune system leads to allergy is vital if we are to develop more effective and efficient treatments for this debilitating condition.”


Dr. Elaine Vickers, Research Relations Manager at Asthma UK, says: “We are delighted to see the rapid progress that Dr. Ghaem-Maghami and his colleagues are making in such a complex area of research.


“This is a great example of where Asthma UK’s research funding is leading to a better understanding of asthma which could ultimately benefit thousands of people with both asthma and allergies.”


Allergy is a disorder caused by the body’s immune system reacting to usually harmless substances found in the environment, known as allergens. Believing itself under attack, the immune system produces a molecule called IgE, which eventually leads to release of further chemicals (including histamine) by certain immune cells which together cause an inflammatory response and the classic symptoms of allergy — itchy eyes, sneezing, runny nose and wheezing.


The Nottingham work, recently published in the Journal of Biological Chemistry, has focused on the role of the mannose receptor (MR), a receptor found on the surface of dendritic cells. These cells are among the first cells in the immune system that come into contact with allergens.


The team recently found that the MR binds to a wide range of allergens and plays an important role in the allergic response to house dust mite allergens. In their latest study they looked at the contribution of MR to allergy caused by a major cat allergen called Fel d 1.


They were able to prove that MR is needed for the body to recognise Fel d 1 as a potential foreign invader and for the production of IgE against Fel d 1. The discovery shows that MR plays a pivotal role not only in recognising but also in provoking the body’s allergic response to them.


Provided by University of Nottingham (news : web)

Banana peels get a second life as water purifier

To the surprisingly inventive uses for banana peels — which include polishing silverware, leather shoes, and the leaves of house plants — scientists have added purification of drinking water contaminated with potentially toxic metals. Their report, which concludes that minced banana peel performs better than an array of other purification materials, appears in ACS's journal Industrial & Engineering Chemistry Research.

Gustavo Castro and colleagues note that mining processes, runoff from farms, and industrial wastes can all put heavy metals, such as lead and copper, into waterways. Heavy metals can have adverse health and environmental effects. Current methods of removing from water are expensive, and some substances used in the process are toxic themselves. Previous work has shown that some plant wastes, such as coconut fibers and peanut shells, can remove these potential toxins from water. In this report, the researchers wanted to find out whether minced banana peels could also act as water purifiers.

The researchers found that minced banana peel could quickly remove lead and copper from river water as well as, or better than, many other materials. A purification apparatus made of banana peels can be used up to 11 times without losing its metal-binding properties, they note. The team adds that banana peels are very attractive as purifiers because of their low cost and because they don't have to be chemically modified in order to work.

More information: "Banana Peel Applied to the Solid Phase Extraction of Copper and Lead from River Water: Preconcentration of Metal Ions with a Fruit Waste", Industrial & Engineering Chemistry Research.

Provided by American Chemical Society (news : web)

Tough crystal nut cracked: Correct prediction of all three known crystal structures of a sulfonimide

  It's not just the type of molecules a material is made of, the way in which they are arranged in space is important too. For many organic molecules, multiple crystal structures are known, and their physical properties can differ significantly. For example, a drug can be effective in one crystalline form but much less effective in another because it doesn't dissolve fast enough. Unfortunately, it has not been possible until recently to reliably predict crystal structures by using computer simulations. Frank Leusen and his co-workers at the University of Bradford (UK) are making significant progress on this front. As the scientists report in the journal Angewandte Chemie, they successfully used a quantum mechanical approach to predict the three known crystal structures of a sulfonamide.


Small differences in the production conditions, such as variations in pressure or temperature, can be enough to cause fine chemicals, such as pharmaceuticals, pigments, explosives, or agrochemicals, to crystallize in a different form. This can lead to problems with the production process or to undesirable product properties. It is correspondingly important to know which crystal structures are possible.


Scientists use computational chemistry methods to obtain information about and crystallization processes. However, taking all of the parameters into account would exceed current computational capacities. “Precise, reliable predictions of the crystal structures of organic molecules have remained somewhat of a Holy Grail for crystallography,” says Leusen.


An international project regularly organizes blind studies in which research groups are asked to predict crystal structures. In 2007, Leusen and two co-workers were able to successfully predict the crystal structures of all four test compounds by using a quantum mechanical approach. A team led by Leusen then took on another test compound, a sulfonamide, which was the subject of a blind study in 2001; none of the participating teams was able to predict the at the time. Interestingly, two additional, previously unknown crystal structures of this sulfonamide were discovered after the study. “By using the computational process developed by Marcus Neumann at Avant-garde Materials Simulation in Freiburg, Germany, we were able to correctly predict all three crystal structures,” says Leusen.


“Even though it is currently not possible to predict the outcome of a specific crystallization experiment under specific boundary conditions,” explains Leusen, “our results demonstrate that precise calculations of the lattice energy are sufficient to model crystallization thermodynamics and thus predict the different crystal structures of small .”


More information: Frank J. J. Leusen, Molecule VI, a Benchmark Crystal-Structure-Prediction Sulfonimide: Are Its Polymorphs Predictable? Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201007488


 



New instrument for analyzing viruses

Scientists in Israel and California have developed an instrument for rapidly analyzing molecular interactions that take place viruses and the cells they infect. By helping to identify interactions between proteins made by viruses like HIV and hepatitis and proteins made by the human cells these viruses infect, the device may help scientists develop new ways of disrupting these interactions and find new drugs for treating those infections.

According to Doron Gerber, a professor at Bar Ilan University in Ramat Gan, the PING system (Protein Interaction Network Generator) can be used to examine thousands of potential interactions at a time, and it detects them at a sensitivity 100- to 1,000-time greater than current methods. Gerber developed PING with collaborators at Stanford University, and he will describe the technology today at the 55th Annual Biophysical Society Meeting in Baltimore.

When a infects a human cell, it hijacks the machinery of that cell, recruiting certain host proteins and subverting them to the task of manufacturing new . This feature of viral biology has made notoriously difficult to treat, as therapies must specifically target the virus without harming the cell.

One approach that has been successful is to identify key interactions between viral and host proteins, which can then serve as targets for . For example, the HIV drug Fuzeon works by blocking a from attaching to proteins on the surface of immune system cells, barring entry to the cell.
Like many antivirals, Fuzeon is used in combination with other drugs in a "cocktail." This is because, like most viruses, HIV mutates rapidly, acquiring resistance to individual drugs. Therefore, the need for new antiviral drugs is constant and ongoing.

Using PING, the Israeli and California scientists identified novel cellular partners for proteins from and hepatitis D. "And we can now use the same system to screen for inhibitors," says Gerber, who adds that new treatments are urgently needed for hepatitis C, for which only one treatment exists that works in only half the patient population.

Because PING employs microfluidics, very small samples can be used; gathering enough material has been a particular challenge with existing methods.

More information: The presentation, "Mapping Virus-Host Protein Interactions Using the PING Microfluidics Platform," is at 5:00 p.m. on Tuesday, March 8, 2011 in Room 307 of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/67lnomy

Provided by American Institute of Physics

Tuned enzymes: Extra guest molecule in an enzyme's binding pocket enables methane oxidation

 Our fossil fuel reserves are limited. When they run out, we will not only be lacking in fuel, but chemical industry will lose its most important feedstock. In contrast, natural gas has barely been used as a raw material. If it were possible to efficiently convert methane, the main component of natural gas, into chemically useful materials like methanol, we would gain some time to make the transition to alternative sources of raw materials.


In the journal , Manfred T. Reetz and a team at the Max Planck Institute for Carbon Research in Mülheim (Germany) have now introduced a new approach for the enzymatic production of methanol from . Their secret is the inclusion of an inert guest in the ’s binding pocket in order to make it smaller so that it can effectively bind methane.


Methanol is a useful starting material for many chemical syntheses, and it can also be added to conventional fuels to drive fuel cells. Conventional processes for producing methanol from methane involve detours (synthesis gas), are markedly complex and energy intensive, and require high temperatures and pressures. Nature, on the other hand, has a much more elegant route: the enzyme methane monooxygenase does the job gently and efficiently. Unfortunately this is a very complex enzyme that cannot easily be produced and used in an artificial environment. The cytochrome P450 (CYP) family of enzymes could represent an alternative starting point. The main job of these enzymes is the oxidation of various substances produced by the body or introduced to it. In the reaction, carbon–hydrogen bonds are oxidized to make alcohol groups (–OH). The active component of these enzymes is a heme, an iron–porphyrin complex similar to that in our hemoglobin.


The problem is that the binding pocket of this enzyme is just too big to snugly bind and oxidize small molecules such as methane. Instead of trying to devise complex methods to create a suitable enzyme, Reetz and his co-workers came up with a clever trick: chemically “tuning” a CYP enzyme. The scientists added an additional guest into the binding pocket in order to make it smaller.


The natural substrates for CYP enzymes are fatty acids. As a guest molecule, the researchers chose a compound that resembles a fatty acid, a carbonic acid in which all of the hydrogen atoms in the hydrocarbon chain have been replaced with fluorine atoms. This type of molecule is as water-repellent as the original, but takes up more room. The fluorine atoms make it chemically inert so that it does not participate in any reactions. Like the molecule it is modeled on, this guest is able to bring the iron–heme complex of the enzyme into its catalytically active state (high-spin state). The significantly smaller binding pocket now allows methane to bind effectively so that it can be oxidized to .


Says Reetz: “The road to success is still far for a technical implementation, yet, the concept opens up new perspectives for the development of further reactions, such as the oxidation of other chemical compounds.”


More information: Manfred T. Reetz, Tuning a P450 Enzyme for Methane Oxidation, Angewandte Chemie International Edition, http://dx.doi.org/ … ie.201006587