Science News - October 9, 2010

Potential uses for artificial amino acids go beyond new medicines, such as getting unusual glimpses of life’s hardware. At

Caltech, Tirrell is flagging proteins with artificial amino acids as the molecules are made, providing the ability to see what product a cell is making at any given time. It’s like having a live video feed of protein synthesis. “This will help us understand how a cell is responding to its environment,” he says.

Drug development

Meanwhile, the Seattle biotech firm Allozyne (founded in part by Tirrell, and using his approach), employs the amino acid substitution method to build a protein that might treat multiple sclerosis.

Schultz hasn’t abandoned the original mission that intrigued him—learning what, if anything, makes the 20 amino acids that nature provides so special. It’s possible that those 20 are the optimal combination. It’s also possible that those are, as the late biologist Francis Crick once described it, part of a “frozen accident” that left people with their current genetic code. Perhaps nature settled on those 20 simply because they offered the first combinations that sustained life at all, not necessarily the combinations that work best. Should other forms of life on distant planets use amino acids, the selection might look different.

As with the growth hormone modifica-
tions, the addition of an unnatural amino
acid may help the mole-
cule — in this case, the MS
drug interferon beta — last
longer in the body, says Ken
Scientists know that they are experi-
menting with some of life’s most basic
Grabstein, Allozyne’s chief
scientific officer. The drug
is in safety tests with vol-
unteers who have multiple
sclerosis, though the results
have not been released.

Like all biologic drugs, those with artificial amino acids raise safety questions: Will the new protein provoke the body’s immune system to attack? So far, Grabstein says, animal studies indicate that the body will accept the new drugs, but this and other questions of safety will not be answered until larger studies are underway.

elements. “Is there a reason we shouldn’t have unnatural amino acids?” asks Church. “Theoretically, you could say that we could make an organism that would out-compete something in the wild.” In other contexts, foreign life has entered natural environments with catastrophic consequences: Asian carp in North American waterways, European rabbits in Australia or kudzu in the American South. Exotic organisms have a history of causing native surroundings to collapse.

remains biologically active for days. The compound is still undergoing testing in people. But at a 2008 meeting of the International Congress of Endocrinology, Ambrx scientists reported on a study of 22 volunteers that found that an injection of the new version can remain biologically active for at least a week.

The company is working on other molecules incorporating unnatural amino acids, including some that could potentially be used to treat multiple sclerosis and diabetes. Another possible chemical attachment is a toxin hooked to an antibody, which zeroes in on a cancer cell to attack it. This method has long been attractive to cancer researchers , but natural proteins have often been too unstable to reach their target before releasing the toxin, Cho says. The hope is that an unnatural amino acid would allow the molecule to hold together longer.

An experimental drug made with human growth hormone (gold) also uses an unnatural amino acid (red).

Church doesn’t think that could happen easily or accidentally — for one thing, left to its own devices, an organism designed to function with an extra amino acid wouldn’t survive if that extra component weren’t around. Nonetheless, Church says, “we should do experiments to see what the consequences would be.” He plans to undertake those in the next few months, by growing an E. coli that requires unnatural amino acids and mixing it with natural strains in laboratory dishes. Most likely, the strain with unnatural proteins won’t survive, even if its extra amino acid is available, but Church won’t know for certain until the experiment is done.

Schultz already plans to see whether life with 21 amino acids fares differently than it does with the usual 20. By next year, he hopes to be able to breed a mouse whose cells can readily use 21 amino acids in daily life. Experiments on a smaller scale have suggested that organisms with 21 amino acids can, in a kind of laboratory-simulated natural selection, develop proteins with extra functions that give them an evolutionary advantage over proteins with 20.

“The 20 amino acids are ideal for proteins that support all life,” says Thomas Magliery, a biochemist at Ohio State University in Columbus. “That doesn’t mean they are ideal for all possible things.” Scientists have spent the past decade making sets of Legos never previously imagined. It’s time now to see what these new blocks will build. 