Quantum Kitteh

see more Lolcats and funny pictures

Antimony for Good Digestion?!

Scribal Terror has an article on "The Everlasting Pill," which was apparently an item you could buy in the past as an aid to good digestion. It was a small "bullet" of metallic antimony that you swallowed as a purgative agent. Not only that, it was meant to be re-used: once it had passed all the way through your digestive system it could be recovered, cleaned off and used again!

The original source is the Medico-Pharmaceutical Critic and Guide (1907), edited by William J. Robinson, which goes on to say:

This, as Dr. J. A. Paris says, was economy in right earnest, for a single pill would serve a whole family during their lives and might be transmitted as an heirloom to their posterity. We have heard of a lady, says the Doctor, who, having swallowed one of these pills became seriously alarmed at its not passing. "Madam," said her physician, "fear not. It has already passed thru a hundred patients without any difficulty."

And then finishes with this keen observation:

We do not think that the everlasting pill would be popular at the present time.

I wonder why antimony was chosen? Antimony and its compounds have been used in treating parasites, but I don't know it that would have anything to do with the supposed "cathartic" properties of the "Everlasting Pill." Of course, antimony is toxic. According to wikipedia, antimony poisoning is similar to arsenic poisoning, which only makes sense since antimony is right below arsenic in the periodic table. I don't know how much metallic antimony you would absorb through the gut, but I doubt it would be a good idea to use this device.

You can read the original, and many other interesting articles in the Medico-Pharmaceutical Critic and Guide which is available by way of Google Books. This book is out of copyright, so you can read the whole thing for free on line, or download a PDF copy for yourself. As a bonus, you can also search and copy selections on line - which is how I got the quote above. Since the PDF version is just a scanned image it can't be searched or copied so easily.

Image: Wikimedia commons

Scribal Terror: The everlasting pill by way of Neatorama,

Anticancer Compound from a Tumor-Promoter

The title of this article caught my eye because of the irony of designing an anticancer drug by modifying a known tumor promoter. Aplysiatoxin is a tumor promoter, while Compound 1 from the paper is not. In fact, Compound 1 is just a simpler version of Aplysiatoxin: the hemiacetal has become an ether and several side groups have been lost. There are also fewer stereocenters in Compound 1 than in Aplysiatoxin.

First a little background. Both compounds affect cancerous cells the way they do because they bind to Protein Kinase C (PKC). PKC is an enzyme that contributes to a number of signaling pathways within the cell, particularly having to do with cell differentiation, proliferation and apoptosis. PKC's involvement in cellular growth cycles also results in its involvement in carcinogenesis, and it has been a target for developing anti-cancer drugs for this reason.

The curious thing about PKC is that some molecules that bind to PKC activate the enzyme, while others de-activate it. Even stranger, some activators promote tumor formation and other activators do not.

PKC activators have shown some promise for treating diseases such as Alzheimers or AIDS, but their tumor-promoting behavior is a big drawback. Ideally you would want to find a PKC activator that was also non-tumor promoting. Bryostatins fit this description, but the compounds are too complex to be easily made in the laboratory. In nature, bryostatins are made by a coral-like organism but in extremely small amounts. According to Wikipedia, you would need a ton (2000 lb) of bryozoans to obtain just one gram of bryostatin.

Aplysiatoxin binds to PCK as a tumor promoting activator. Compound 1 was designed as a simpler version of aplysiatoxin that might be a PKC activator without also being a tumor promoter. As it turns out, compound 1 shows minimal tumor-promoting activity, and it counteracts the effects of the tumor-promoter 12-O-tetradecanoylphorbol-13 acetate. It's anti-cancer activity as well as it's mode of binding to PKC seems to be comparable to the bryostatins. The authors report that they can make Compound 1 in only 22 steps, which makes it a promising alternative to bryostatins as a potential therapeutic agent.

Nakagawa, Y., Yanagita, R., Hamada, N., Murakami, A., Takahashi, H., Saito, N., Nagai, H., & Irie, K. (2009). A Simple Analogue of Tumor-Promoting Aplysiatoxin Is an Antineoplastic Agent Rather Than a Tumor Promoter: Development of a Synthetically Accessible Protein Kinase C Activator with Bryostatin-like Activity Journal of the American Chemical Society, 131 (22), 7573-7579 DOI: 10.1021/ja808447r

Lord of the Rings Webcomic

I came across "DM of the Rings" on Neatorama the other day and had to read all 155 installments. It's a hilarious web comic by Shamus Young that uses scenes from the Peter Jackson Lord of the Ring movies to imagine a group of Dungeons & Dragons players reenacting the Lord of the Rings. Needless to say the players haven't read the book (or seen the movies), and while D&D is a role-playing game, the players have a hard time staying in character.

The first episode is a good place to start. As a science geek, I particularly liked Schrödinger’s Familiar. If you aren't familiar with the gazillion monsters character might run into, a Lich is a sort of undead sorcerer.

The Chemistry of Firework Displays

photo credit Dori (Wikimedia Commons)

Slashdot has links to some cool articles on the chemistry of Fireworks.

Slashdot News Story | The Chemistry of Firework Displays

Ridiculous Fellows: Amazing Organ Performance

"Ridiculous Fellows," from Prokofiev's "The Love for Three Oranges" orchestral suite. Qi Zhang playing a Yamaha Electone Stagea, which she programmed herself.

Quorum-Sensing Molecules

I was fascinated by Bonnie Brasler's TED talk on Quorum-Sensing, and being a chemist I wanted to know more about the molecules involved. She did put up a slide with structures during the talk, but I wanted more so I did a search on PubMed and found this Perspective written by Brassler and Michael Federle.

My only experience with the notion of a “quorum” is our Faculty Assembly where we sometimes have difficulty achieving a quorum. In order for the meeting to be “official” and for any votes taken to be valid we need to have a minimum number of faculty present, a “quorum.” For bacteria, quorum sensing is the way the bacteria “count” one another. The bacterium releases a particular molecule, called an autoinducer - if there are lots of the molecules, then there are a lot of bacteria. If there are very few autoinducer molecules, then there are few bacteria present. The bacteria has a protein receptor that binds to the autoinducer molecule – so the bacteria can “sense” the presence or absence of autoinducer molecules depending on whether or not the receptor protein has detected any. In this way the bacteria can change their behavior depending on the number of bacteria present, as measured by the number of autoinducer molecules it finds. As a group, the bacteria behave one way when there is a low density of bacteria present and a different way when there is a high density of bacteria present.

In the simplest examples, quorum-sensing allows the bacteria to switch between two different behaviors depending on the number of bacteria present. One example would be the staphylococcus aureus bacteria – at low density they adhere to the surface of the cells of the host organism where they can grow and produce more bacteria. Once they reach a “quorum” there are enough bacteria present to be able to invade the host cells Their metabolism then shifts from producing the proteins that allow attachment to the outside of host cells and starts to produce proteins and toxins that allow the bacteria to enter the host cells. The light-producing bacteria from Bonnie Brassler's TED talk produce light when there are a lot of bacteria present, and stop producing light when there are few bacteria present.

Enough about biology, what about the molecules involved? In this Perspective, two categories of autoinducers are discussed, and one “special case.” Gram negative bacteria produce a type of autoinducer referred to as AHL for Acyl Homocysteine Lactone. Different types of bacteria will have different acyl groups attached to the homocysteine, and only recognize their own type of AHL. Gram positive bacteria do not use AHL's, instead they produce specialized proteins called AIP for AutoInducing Peptides, which consist of a string of 5 to 17 amino acids, some of which may be modified. The two types of autoinducer (AI) are detected by the bacteria when the AI binds to a receptor molecule in the bacteria. The details differ, but when enough AI's are around to bind to their receptors, the receptor causes a change in gene expression in the bacteria, which leads to a different behavior by the bacteria. 

The AHL's and AIP's are species specific: each type of bacteria produces only one AI and only recognizes it's own AI. The third type of molecule discussed is an unusual boron-containing molecule that may have a role for communication between different species of bacteria. The light-producing bacterium vibrio harveyi produces two different autoinducer molecules. The first is referred to as AI-1. AI-1 is an AHL molecule used for communication only among the V. harveyi bacteria. The other autoinducer is AI-2 which, on the other hand, may have a role in allowing different species of bacteria to communicate with one another.

AI-2 is synthesized by the bacteria in three steps from S-adenosyl methionine. The enzyme for the final step in this synthesis is called LuxS and as it turns out the gene for LuxS is found in many different bacteria, which all seem to both make and respond to the presence of AI-2. The implication of this is that perhaps AI-2 serves as some sort of generic autoinducer that allows bacteria to sense not only their own species, but also all other species of bacteria that produce AI-2.

The really interesting thing is that if we understand how bacteria communicate, we can find ways to short-circuit that communication. Many pathogens use quorum-sensing to regulate their virulence. In the example I mentioned earlier about S. aureus, the bacteria depend on reaching a “quorum” before they begin to “invade” the host cells. If their ability to sense one another is prevented, then perhaps their ability to invade the host and cause disease could be reduced.

Federle, M. (2003). Interspecies communication in bacteria Journal of Clinical Investigation, 112 (9), 1291-1299 DOI: 10.1172/jci200320195