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'Lego' Approach Thwarts Anthrax Toxin
NewScientist is reporting that scientists have discovered complex nanoscale structures that have successfully protected rats from anthrax. From the article: "The technique relies on using tiny 'peptide' molecules, stuck onto one large molecule, which bind to toxins and prevent them from causing damage. They do this in much the same way that two Lego bricks might fit together - with several studs from the binding molecule slotting into, and so blocking, the sites on a toxin molecule which are needed to cause damage."
That's the way EVERYTHING in biochemistry works!
Doesn't Lego have a patent on the whole block stacking concept? Looks like they're in for a legal battle on this one. :)
All I know is, know one has truly known pain until they have been barefoot and stepped on one of these molecules.
I judt got a nre Kinesis keybiartf so please excusr ant egregiou typos.
With mint frosting?
stuck onto one large molecule, which bind to toxins and prevent them from causing damage.
That's called an antibody.
Leela: I didn't want to leave them either Fry but what are we supposed to do?
Fry: Well, usually on the show someone would come up with a complicated plan then explain it with a simple analogy.
Leela: Hmm. If we can reroute engine power through the primary weapons and reconfigure them to Melllvar's frequency that should overload his electro-quantum structure.
Bender: Like putting too much air in a ballon!
You just used the word LEGO to make me read this! LEGOs have about as much to do with this molecule binding as a bowl of petunias does!
Shares of Lego, Inc. go through the roof as hudreds of thousands of biochemists rush to buy Lego products. The question is, which theme will help their research more? The pirate sets or the Star Wars sets? My money's on Star Wars.
Mr. Bond, they have a saying in Chicago: Once is happenstance. Twice is coincidence. The third time is enemy action.
TFA is light on detail, what a surprise, but I am guessing the novelty here is that you can in some cases get the advantage of multiple-binding cooperativity without having to custom-design the molecular backbone "scaffold" that holds the binding sites in the correct relationship. By just changing the density of peptides on the surface of the liposome, they can more or less continuously "tune" the distance between the binding sites. So, in principle, the advantage to this kind of approach would be that you could rapidly and cheaply create many different antagonists for many different poisons. It's hugely cheaper to just vary the density of peptide binding sites on your liposome than it is to synthesize a whole range of molecular backbones to hold the peptide groups in different arrangements.
Also...a biochemist may want to correct me, but TFA says that these buggers bind toxins "thousands" of time better than free peptides. But to be seriously effective, wouldn't you need hundreds of thousands or even millions of times better binding? After all, you don't want to have to feed your patient as much of the antagonist as they gave these poor rats: 500 mg for a 300 g rat is a dosage of 1.7 grams/kilo of body weight! A normal man (65 kg) would have to have over 100 grams of the stuff injected into him. That's an absurd amount of medicine and is bound to have deleterious side effects.
Great! Just put about a thousand 4-year-olds in a room with a whole bunch of Lego blocks, and a huge molecular model. You don't even have to tell them what to do. Just continuously monitor the state of the room with video cameras, and once they have designed an appropriate antibody, encase the whole thing in carbonite.
Monsanto, here we come!
Two different studies, coming to conclusion this week.
Now, along with the anthrax killer protien, we are making progress, indeed.
Whats more, this protien looks to be anti-resistant too.
rajmohan_h@yahoo.com
It's nice to be able to make them to order for formerly untreatable disseases.
Friends don't help friends install M$ junk.
It's more of a prove of the authors incompetence.
Peptides are certain linked molecules. "Peptide" is an scientific expression for "linked aminoacids", nothing more, nothing less.
Putting it in quotes is as if you put "computer" or "internet" in qoutes. You make obvious your neither part of "the scene" nor have a clue what you're writing about.
The scientists knew that certain protein shapes could bind to toxins produced by the anthrax bacteria. They've found that embedding the proteins in liposomes, which are vesicles comprised of a phospholipid bilayer just like ordinary cell membranes, significantly increased their effectiveness. They've figured out how high of density of proteins to embed in the liposome surfaces so that the distance between proteins matches up with bonding sites on the toxins, forming a stronger bond and a better chance of bonding to begin with.
In their control group, 8 out of 9 rats given the toxin (not the actual anthrax bacteria, though) died. In the test group, only 1 of 9 rats given the toxin plus 500 mg of the protein-embedded liposomes died. Since the protein only targets the toxin, the treatment would have to be used in conjunction with antibiotics to kill the bacteria. There is no mention in the article whether the toxins and liposomes are flushed out of the body or broken down, but the end result is that the toxins can't bind to whatever it is they normally do to cause trouble.
Liposome probably isn't a familiar term, so look up liposome or cell membrane (includes drawing of embedded proteins) if you want to get a better understanding. Wikipedia has a decent article on anthrax, but I googled and found a much better write up from the University of Wisconsin that might help you get a good "big picture" look at what goes on.
From my reading it looks like there are multiple toxins. One causes septic shock through a method that is apparently not yet fully understood. It bonds to a protein in the cell membrane (just like the proteins in the liposomes), and interferes with cellular signalling. Fascinatingly, two other toxins actually cause ATP depletion and swelling in phagocytes (a particular type of cell in the immune system) so that they aren't able to engulf the anthrax bacteria and break them down. It's like a biological counter-countermeasure. Not karma whoring...I just thought after I'd looked up all that information some other people would be interested, too. All this reminds me why I enjoyed biology so much back in high school.
To give a balanced answer: Yes and No.
Many drugs work by binding to a target protein and inhibiting its activity in this way. However, there are several ways to achieve this. The conventional form of drug is a "small molecule", created by organic chemistry. These are called small because they are much smaller (and less complex) than proteins -- say more than a factor 10 smaller.
Small molecules can have enormous advantages: They are relatively easy to manufacture and to store, and if they are stable enough and well absorbed, they can be taken orally. If you want something simple and cheap for large-scale use, a small molecule is the way to go. However, the downside is that they are very complex and expensive to develop.
The other big category is that of the "biologicals", which includes proteins and peptides -- a peptide is essentially a small fragment of a protein, but still bigger than a small molecule. Antibodies are a category of proteins; in the case of antibodies, development is relatively easy because the body produces them naturally. There is also the possibility of taking a protein's natural binding partner, and then synthesising this on a large scale to outcompete the natural binding partner. The general expectation is that biogicals will be easier to develop than small molecules and for many diseases, will be the first form of treatment available.
The typical disadvantages of biologicals are that they need to be stored in a freezer, must be injected rather than swallowed or inhaled, and are expensive to manufacture. This usually restricts their use to relatively small numbers of patients, in hospital environments or receiving intense attention from their physicians. (Insulin is a well-known exception, however.)
Some people believe that small molecules are fundamentally unable to block certain interactions. The reasoning is that that something small can only attach efficiently to a target site if the available forces on that site are large enough, i.e. if there is a so-called "pocket" to fit the molecule in. While biologicals, because they are bigger, can bind over a wider area, so can be effective even if smaller forces are involved.
In this case, the scientists took peptides, which are relatively small, but instead of combining them into an actual protein (which would have been very complex and expensive) they grouped them together on the surface of a liposome, which essentially is a tiny droplet of fat. And the observation is that indeed, the interaction of the multiple peptides with the target still adds up, giving the liposome a much stronger binding to its target than the individual liposomes.
This creates numerous interesting possibilities. This might work with small molecules as well as peptides, for example; or you might even combine the two in a single treatment.
Yes, it can happen. Look for a example at recent drug trial incident in London, where a therapeutic antibody that had good results in animals (and apparently mild side-effects in monkeys) had dramatic and potentially fatal side-effects in human volunteers.
The effects are rarely that dramatic, as the worst effects are usually discovered in animal trials. (For added safety, at least two species are used, one rodent and one non-rodent.) However, unwanted side effects are the rule rather than the exception, and the only really reliable way to find out so far is through tests on human volunteers. Most drugs do fail in these trials!
Actually, even the drugs that do pass the clinical test stage and are approved rarely work for all patients. The FDA is happy if the drug helps a sufficiently large fraction of patients, and does not real harm except in exceptional cases. It is the average cost-benefit that counts, not the result for the individual patient, which is at this moment often impossible to predict.
For there is genetic patient-to-patient variation among humans as well, not to mention genetic variation among pathogens, and a drug that fits the protein in the body of patient A may fail to do so in patient B. And a drug that does A and B no harm may have fatal effects in patient C.
Genetic targeting of drugs has already caused a controversy around NitroMed BiDil, a heart medicine that is specifically effective for black patients — admittting that few Americans are of pure genetic "African" or "Caucasian" stock. The culturally acceptable (but scientifically dubious) solution is to allow patients to "self-identify" as black and therefore potential users.
For the future much hope is put in "personalized medicine", giving the patient a genetic analysis first to determine whether a drug would be really effective — or would have serious side effects. However, this too has obvious cultural and moral problems attached to it.