Synthetic Molecules Emulate Enzyme Behavior

FiReaNGeL writes "Ohio State University chemists have created a synthetic catalyst that can fold its molecular structure into a specific shape for a specific job, similar to natural catalysts. In tests, the chemists caused the catalysts to twist one way or the other, either to form one chemical product or its mirror image. They confirmed the shape of the molecules at each step using techniques such as nuclear magnetic resonance spectroscopy. Being able to quickly produce a catalyst of a particular shape would be a boon for the pharmaceutical and chemical industries."

Comments

a hint of deja vu

[janneH]

Anyone remember catalytic antibodies - from 20 years ago - which also promised rapid engineering of "enzymes" for specific reactions. They were made by immunizing an animal with a transition state analog - under the theory that stabilizing the transition state would speed up reactions (since that is what enzymes do). Well, these "abzymes" completely revolutionized enzymology and biotechnology.....oh, wait...

Re:a hint of deja vu

[Rev_Frozt]

I think this is fairly clearly overhyped. They are suggesting the following:

We can construct more flexible molecules to use as catalysts. More flexible molecules interact more easily with other molecules in the environment. Unfortunately, by reacting without selectivity, it is more likely to find unexpected side-effects. This would have no place in drug design, though it could plausibly be used in very controlled environments. Realistically, people tend to want a catalyst to take A->B, not to take A-B, C-D, E-F, G-H, B-A, etc. The laundry list of reactants makes it more difficult to control or contain the reaction and makes the "enzyme" itself more dangerous to handle. There may be some utility to this in the long run; however, at present it appears as though their chief accomplishment can be summed up in one sentence:
"We have come up with a (complex) way to take a very simple, easy to use enzyme like TAC Polymerase and turn it into something with unknown side-effects that may or may not function as expected."

This just looks like buggy code to me... I mean, consider Polymerase as an example. It works well because it binds very specifically to DNA and matches appropriate base pairs. If it had a significantly more flexible binding pocket, and was less choosy, what use would it really be? Who wants to use a polymerase with a high probability of generating "AAAAAAAAAAAA..." regardless of the source strand used as a basis? Who wants a transport mediator protein without directionality? I mean, the idea translates to "let's take known algorithms and just give a non-0 probability of incorrectly jumping at any control point to see what happens". I think it is clear that most algorithms just fail if someone so much as flips an if -- imagine if they removed, flipped, or added random ifs every time the algorithm was run...

Yadda yadda more analogies...

This is cool on many levels.

[slimjim8094]

At some level, it was only a matter of time: put the molecules together in the right order, and (generally) the form the right shape when left to fold by themselves.

But synthesis of enzymes and such has interesting ramifications for medicine (can't think of any enzyme-deficient diseases off the top of my head, but there must be some)

Now what would be *really* interesting is if they could do proteins in general. That would open up a whole world of life-saving drugs.

I'm skeptical

[Sethumme]

IANAC, but TFA seems to overstate the find and contains several misleading statements.

First, they cannot "quickly produce a catalyst of a particular shape," but rather they are able to take one molecule and make it twist into either of two orientations. This isn't the holy grail of catalyst molecular engineering (to "give scientists a quick and easy way to get the catalyst that they want"); rather, it gives scientists a couple 'bonus' molecular shapes for each catalyst they synthesize. There is no indication that the ability to twist synthetic molecules means that scientists will have a significantly easier time discovering new catalysts that conform to the necessary shape. As TFA says, "[d]espite decades of research, scientists aren't sure exactly how this kind of propagation works." Why should searching for "a catalyst of a particular shape or function," involve any less trial and error than before?

Moreover, the scientists claim that "as long as there is even a slight chemical preference for one of the hands. . . . [t]he 'flexible glove' will find a way to make a better fit, and so it will assist in specifically making one of the mirror image forms." Yet there is no proof that this "chemical preference" necessarily results in the ideal molecular arrangement of the catalyst. In fact, trying to synthesize a molecule that is capable of folding into multiple useful shapes in response to specific chemical environments seems more difficult than synthesizing individual catalysts to each handle one function independently.

Again, I could be wrong, but I think this is only a very preliminary step in making more advanced synthetic catalysts, and not necessarily a way to design them faster.

Re:Yay!

[Tubal-Cain]

Pharmaceutical companies can only sell a cure once. They can sell treatments indefinitely.

Re:Yay!

[Veggiesama]

Why does everybody always say this, hinting about the possibility of conspiracy theory cover-ups and withheld cures? Why is it so hard to believe that some people actually are searching for cures?

If a company develops a cure for AIDS, cancer, or the common cold, then it stands to reason that the company is going to make a lot of money. While other companies are bumbling around with "treatments" and "therapies," this company is going to make a lot of short-term profit, and with the help of a patent office (or whatever equivalent), AFAIK they'll retain that virtual monopoly for decades to come.

And if you can count on capitalism for anything, it's short-term gains.