New field of chemistry has potential for making drugs inside patients -- and more

The traditional way of making medicines from ingredients mixed together in a factory may be joined by a new approach in which doctors administer the ingredients for a medicine separately to patients, and the ingredients combine to produce the medicine inside patients' bodies.

That's one promise from an emerging new field of chemistry, according to the scientist who founded it barely a decade ago. Carolyn Bertozzi, Ph.D., spoke on the topic -- bioorthogonal chemistry -- in San Diego on March 27 in delivering the latest Kavli Foundation Innovations in Chemistry Lecture at the 243rd National Meeting & Exposition of the American Chemical Society (ACS).

Bertozzi explained that the techniques of bioorthogonal chemistry may fundamentally change the nature of drug development and diagnosis of disease, so that the active ingredients for medicines and substances to image diseased tissue are produced inside patients.

"Suppose a drug doesn't reach diseased tissue in concentrations high enough to work," Bertozzi said, citing one example of the potential of the new chemistry. "Maybe it is an oral drug that doesn't get absorbed very well into the blood through the stomach. You can imagine a scenario in which doctors administer two parts of the molecule that makes up the drug. The two units reach diseased tissue in large amounts or get absorbed through the stomach just fine. Then they recombine, producing the actual drug in the patient's body. Bioorthogonal chemistry is chemistry for life…literally!"

Bertozzi explained that bioorthogonal chemistry opens the door to creating new proteins, fats and sugars directly inside living cells without harming them. The field emerged from her frustration in the late 1990s with the lack of tools available to see sugars on the surfaces of living cells. Chains of these sugars, called glycans, sit on the surfaces of cells in the body and control the doorways through which different molecules enter. When a disease-causing virus enters and infects a cell, for instance, proteins on the virus's surface attach to certain glycans.

"To do that, we had to come up with a chemical reaction that would be really selective, only targeting the sugar of interest and the fluorescent probes that we delivered to it," said Bertozzi. The chemicals also couldn't stick to other biomolecules that the researchers didn't want to see.

That turned out to be a tall order, indeed. "We pulled all of our big textbooks off the shelves and flipped through them to see if there was something out there that fit our criteria," she said. Those criteria were essentially the conditions inside a living cell or living organism such as a mouse -- a reaction that could occur in water at pH 7 and at 98.6 degrees Fahrenheit. The reaction also couldn't interfere with all the other biomolecules in a cell or organism that keep it alive.

"It was a pretty restrictive set of conditions that a traditionally trained organic chemist like me never had to work within," she explained. That's because these types of reactions are usually performed in very clean, dry test tubes and flasks under conditions that the chemist can control. A living cell or organism, with all its water, proteins, fats, sugars and metabolites is very messy and uncontrollable by comparison.

Bertozzi and her team at the University of California, Berkeley, went on to develop a slew of reactions that can add fluorescent labels to biomolecules.

Now, the field is exploding, with her group and others reporting new bioorthogonal chemical reactions every year that help researchers see sugars, fats, proteins, and even DNA and RNA, that can't be seen using conventional methods. Researchers currently use the reactions not only to see where a biomolecule is within a living cell or organism, but also to determine when a biomolecule is made and what it binds to. Researchers also are using the methods to add things besides labels, like drugs, to various biomolecules. Some of the chemicals used for the reactions are currently available separately or in kits.

Several of Bertozzi's reactions are patented, and some are licensed to companies, including Redwood Bioscience, a company she co-founded with David Rabuka, Ph.D. The company is focused on bringing this technology to the clinic.

The scientists acknowledged funding from the National Institutes of Health and the Howard Hughes Medical Institute.

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The above story is reprinted from materials provided by American Chemical Society (ACS), via Newswise.

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To boldly go where no glass has gone before

Dr Castillo said the special glass will be the first QUT project to be launched into space.

"True ZBLAN glass fibres can only be made in the absence of gravity," he said.

"This glass contains a variety of heavy metals that upon cooling create internal stresses which leads to crystallization of the material, an undesired property for glass.

"The synthesis of this material in the absence of gravity has the ability to overcome this barrier."

It is believed the glass could revolutionise the way we make fibres for telecommunications and medical imaging tools.

Dr Castillo said the glass has the lowest theoretical attenuation loss of any glass yet known to man, which means little or no loss in signal occurs within the material.

"This special glass can be potentially drawn into a solid fibre and signals would be able to be transmitted over much great distances than in current silicate glass fibres," he said.

"The result of this is potentially eliminating power consuming amplifiers and repeaters while significantly increasing bandwidth.

"Although this glass has been made in a few places, no one has yet figured out how to draw it into a fibre."

Research will first be conducted at QUT's micro-gravity tower in an experiment that will see the glass undergo ~2.1 seconds of microgravity over a 21.3 meter drop inside a drag shield.

Dr Castillo, who has previously worked for space programs in the United States and Japan, will then board NASA's parabolic flight plane, dubbed the 'vomit comet', before launching the project into space via a United States Air Force suborbital satellite by mid next year.

"In order to stay at the leading edge of the synthesis of specialised glass, all traditional methods have to be abandoned," Dr Castillo said.

"I previously spent two years working in Japan trying to produce this glass via gas levitation and with a fibre pulling apparatus in zero gravity and was unsuccessful.

"Now I think we've been able to formulate very new and different techniques to that used by anyone in the world."

Provided by Queensland University of Technology (news : web)

A 24-karat gold key to unlock the immune system

Using nanoparticles made of pure gold, Dr. Dan Peer, head of Tel Aviv University's Laboratory of Nanomedicine at the Department of Cell Research and Immunology and the Center for Nanoscience and Nanotechnology, with a team including Drs. Meir Goldsmith and Dalit Landesman-Milo and in collaboration with Prof. Vincent Rotello and Dr. Daniel Moyano from the University of Massachusetts at Amherst, has developed a new method of introducing chemical residues into the immune system, allowing them to note the properties that incur the wrath of immune cells. Because the gold flecks are too small to be detected by the immune system, the immune system only responds when they are coated with different chemical residues.

This breakthrough could lead to an increased understanding of the properties of viruses and bacteria, better drug delivery systems, and more effective medications and vaccinations. Their study was published in the Journal of the American Chemical Society.

A tool for exploration

To begin probing the immune system, researchers used particles of gold, approximately two nanometers in diameter, and covered them with various chemical residues. Only when water-resistant residues were introduced did the immune system respond to their presence. That established a demonstrable link between hydrophobicity — the degree to which a molecule repels water — and the reaction of the immune system.

This idea has a basis in the normal functioning of the immune system, Dr. Peer explains. During cell death, the hydrophobic areas of the cell membrane become exposed. The immune system then realizes that damage has occurred and begins to alert neighboring cells.

The researchers discovered that the same principle held true for the chemicals added to the gold particles' surface. The more "water-hating" the particle is, the more actively the immune system will mobilize against it, he says.

Dr. Peer observes that this is only the first step in a long line of experiments. "We are using these gold particles to tackle the question of how the immune system recognizes different particles, which might include features such as geometry, charge, curvature, and so much more. Now that we know the tool works, we can build on it," he says.

Testing the "Danger Model"

Until now, scientists have developed theories about how the immune system functions, but have lacked the machinery to test these ideas. One such theory is the "Danger Model" by Prof. Polly Matzinger, which hypothesizes that cellular damage interacts with immune cells at the membrane level. Once they identify the foreign molecule as a "danger," the immune cells send signals throughout the immune system. Their initial experiment with hydrophobicity was designed to generate a toolbox for probing this theory, says Dr. Peer, whose investigations included both in vitro and in vivo experiments using mouse immune cells.

In the future, researchers will study various bacterial, viral, or damaged cells and to make the gold nanoparticles even more similar, thereby discovering which elements of dangerous particles are calling the body's immune system to arms. "We now have the capability of using nanomaterials to probe the immune system in a very accurate manner," says Dr. Peer, a breakthrough that could revolutionize the way we understand the immune system.

Provided by Tel Aviv University (news : web)

Study on swirls to optimize contacts between fluids

 A new model gives clues on how to optimize homogeneous feeding of cells in suspension from a liquid nutriments supply in a bioreactor.

Physicists who have studied the mixing between two incompatible fluids have found that it is possible to control the undercurrents of one circulating fluid to optimise its exposure to the other. This work, which is about to be published in EPJ E1, was performed by Jorge Peixinho from CNRS at Le Havre University, France, and his colleagues from the Benjamin Levich Institute, City University of New York, USA.

The authors compared quantitative experimental observations of a viscous fluid, similar to honey, with numerical simulations. They focused on a fluid, which partially filled the space between two concentric cylinders with the inner one rotating. This system was previously used to study roll coating and papermaking processes. To interpret this seemingly simple system, they factored in interface flows, film spreading, and the formation of free surface cusps -- a phenomenon relevant to fluid mixing, but which is not quantitatively captured by conventional numerical calculation.

The authors observed the presence of several flow eddies, stemming from fluid flowing past the inner cylinder, causing it to swirl, and the appearance of reverse currents including one orbiting around the rotating cylinder and a second underneath. They made the second eddy disappear by increasing the fluid filling or its velocity. This is akin to turning a spoon full of honey fast enough to prevent it from draining.

This model is based on a highly viscous oil combined with air as a top fluid. When combined with a light oil containing nutriments as a top fluid, it could also apply to a suspension of bioreactor cells typically used to produce biotech medicines. Ultimately, it could help identify the right parameters and adequate mixing time scales to ensure that nutriments feed all the cells homogeneously without segregation.

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The above story is reprinted from materials provided by Springer Science+Business Media, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:

Peixinho J., Mirbod M. and Morris J.F. Free surface flow between two horizontal concentric cylinders. European Physical Journal E, 2012 DOI: 10.1140/epje/i2012-12019-8 2