In today’s issue of Science, there’s a nice review on protein dynamics by Mittermaier & Kay and a paper on the dynamics and function of a peptidyl carrier protein domain of tyrocidine A synthetase. In their review, Mittermaier & Kay wrote:
Recent methodological advancements in NMR have extended our ability to characterize protein dynamics and promise to shed new light on the mechanisms by which these molecules function … NMR spectroscopy is uniquely suited to study many of these dynamic processes, because site-specific information can be obtained for motions that span many time scales, from rapid bond librations (picoseconds) to events that take seconds.
Although I’m sure X-ray crystallography will still be widely used to determine the three dimensional structures of proteins in the future, I think we’ll start to hear more about the utility of NMR spectroscopy, especially since there are a number of NIH-funded structural genomics centers that are using NMR spectroscopy to solve protein structures, there are new labeling methods that may make it possible to use NMR to solve the structures of larger proteins, and there are exciting demonstrations of how solid-state NMR can be used to probe the structure and function of membrane proteins.
NMR can also be used to find important biologically active small-molecules/potential drugs – for example, Oltersdorf et al. used NMR to find and optimize a new anti-cancer compound and Forino et al. used a “fragment-based approach” to find a new inhibitor of the lethal factor metalloproteinase from Bacillus anthracis.
Of course, many of these experiments can’t be done on an aging NMR spectrometer. In a recent Nature paper, Dorothee Kern’s group used a Varian 800-MHz spectrometer to examine the dynamics of the prolyl cis–trans isomerase cyclophilin A. 800-MHz spectrometers will need to get a lot cheaper before many laboratories can afford to use them routinely…
Joshua
Joshua Finkelstein (Associate Editor, Nature)
[Editor’s note – I’m fairly sure this comment was intended for the ‘Facing up to fullerenes’ entry and so it has been included there as well]
I have also been working with C60 for years, and to everyone I know it is accepted as pretty benign – you don’t worry at all about getting on your hands for example.
As to the substance behind the Zelens, there is actually a lot of scientific support for the antioxidant activity and safety. Notably, the fact that Merck licensed a water soluble C60 derivative in 2003 for continued study as a neurological antioxidant. There are literally dozens of patents and applications on the use of C60 compounds as antioxidants, and dozens more on the antioxidant activity. This all began at DuPont in about 1991 – where they showed the enormous capacity of a C60 to soak up fullerenes, and they coined the phrase “radical sponge” at that time. Not shoddy science, and it has been verified over and over again by leading scientists in peer-reviewed publications.
Mitsubishi has also been intensively studying the safe application of C60 compounds as antioxidants, and formed a company in Japan, Vitamin C60 Bioresearch, to market fullerene-containing skincare formulations. They’ve been doing quite well. They also have published several peer-reviewed articles on the safety.
So, knowing the literature quite well on the physiological application of C60 compounds – there is beyond the shadow of a doubt a great potential for the use of C60 as a safe antioxidant (a lot of toxicity data is out there), and believe it or not, Zelens is not the only product out there. Several more already exist in addition to Mitsubishi.
As to the recent Rice work, it is a travesty since they studied not C60 but 10 – 20 nm particles of C60, which has also been shown to have tetrahdrafuran inclusions which could have caused their observed oxidation of cell walls. A very recent publication from Japan duplicated their study using the same material as used in the Rice study but without THF, and they observed no adverse toxicity.
Whether Zelens or Mitsubishi actually have enough fullerenes in their product to actually do anything beneficial (or to be worth the money) is a different question, and I can’t vouch for either product.
By the way, the going price for pure C60 is about $25/g – just a shade higher than gold.