The Alchemist Newsletter: February 13, 2007

In The Alchemist this week, counter weapons against botulinum toxin, how a little squirt could fight cancer, melting poles leads to liquid magnetism, volcanic catalysts, and how artificial proteins could do a better job than the real thing.

	bioweapons: Botulinum counter attack
	pharma: Little squirt fights cancer
	physical: Melting poles
	geochem: Volcanic catalysts
	biotech: Artificial proteins

Botulinum counter attack

Two compounds that could act as anti-toxins against the botulinum neurotoxin, have been identified by US researchers. The finding could provide a potential defense against botulinum used in biological terrorism or in cases of botulism. Clostridium botulinum produces lethal paralysis-inducing neurotoxins, but high production costs of the "antidote" and severe side effects mean it is not readily available nor widely used. Now, Kim Janda and colleagues at the Scripps Research Institute have identified several compounds and tested their efficacy in both cell-based assays and in mice exposed to the toxin. The second favorite increased time to death by 36%, while 16% of animals treated with a second molecule survived with no obvious symptoms. The compounds showed little activity in the cell-based assays, suggesting that standard cell-based screening methods may miss potential candidates. The two compounds could be used as a cocktail therapy, Janda says.

Compounds show significant promise against potential bioweapon toxins

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Little squirt fights cancer

The seasquirt Diazona angulata anchors itself to rocks in the Philippines and manufactures a toxin called diazonamide A to ward off predators. That toxin just happens to kill cancer cells. Now, researchers at the University of Texas Southwestern Medical Center have modeled a new drug on this toxin that also kills cancer cells. Unlike its natural counterpart it does not harm healthy cells, which could make it a more useful drug. Team leader Patrick Harran says this molecule has a unique mode of action and is "teaching us more than we imagined". The structure of diazonamide A was first reported in 1991, but in 2001, Harran's team showed the initial assignment to be wrong and published the correct structure. He and his colleagues found that the toxin interacts with the cellular metabolic enzyme OAT, which was known to be involved in cellular metabolism but had no previously known role in cell division. However, it does not simply inhibit this enzyme but instead revealed that the enzyme has a second role, in cell division; hence the anticancer activity.

Toxin found to attack cancer, not healthy cells, in mice

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Melting poles

We normally think of magnets as solid objects, but the Earth's core is molten and generates a magnetic field from the very flow of the liquid metal of which it is composed. Now, researchers at the ƒcole Normale SupŽrieure (ENS) institutes in Paris and Lyon and the Atomic Energy Commission (CEA) in Saclay have demonstrated that it is possible to create a self-sustaining magnetic field in laboratory experiments even if the fluid flow is highly turbulent. The researchers explain their experimental design offers a realistic simulation of the Earth's dynamo than earlier experiments because the fluid is free to flow in a large tank rather than being channeled using baffles or tubes to mimic the movement of the earth's core. Their results will help scientists better understand magnetic fields in planets and stars.

Molten metal magnet

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Volcanic catalysts

Researchers in Germany have used igneous rock from the outpourings of Mount Etna to catalyze the formation of carbon nanotubes. Dang Sheng Su and colleagues at the Fritz Haber Institute in Berlin have found naturally occurring iron oxide particles in lava make it an effective natural catalyst. The work opens up a renewable and cheap approach to mass producing nanotubes and nanofibers. Crushing of iron oxide rich cooled lava and high temperature treatment with hydrogen gas, reduces the oxide to nanoscopic particles of iron oxide, which can template the deposition of carbon from a hydrogen-ethylene gas mix at relatively moderate temperatures. Their work also points to the possibility that, given the presence of methane and hydrogen in volcanic gases, carbon nanotubes might form naturally in volcanoes or on extraterrestrial worlds.

Lava is used to make carbon nanotubes

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Artificial proteins

Building artificial proteins from synthetic amino acids not found in nature could lead to an entirely new class of orally active drugs that mimic real proteins but are not digested in the gut or targeted by the immune system. Alanna Schepartz of the Howard Hughes Medical Institute and her team have synthesized several beta-amino acid monomers to use as building blocks for a synthetic protein. Beta-amino-acids exist in the cell but are never incorporated into proteins naturally. The team then used these building blocks to construct a beta peptide chain, which they found could fold in a manner resembling an alpha chain. They used X-ray crystallography to show that their beta peptide, known as Zwit1-F, folded into an active well-defined bundle of helices. The work not only has implications for novel drug types but raises the eternal question of why nature does not use beta amino acids to build proteins, instead using almost exclusively the alpha forms.

Man-made Proteins Could Be More Useful than Real Ones

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-- David Bradley, Science Journalist