Zerhouni Steps Down

I just received this email today from the NIH. The Bush appointed director of the National Institutes of Health is stepping down in October.

Dear Friends and Colleagues in the extramural community,

Today, I informed my NIH colleagues, including staff, scientists, administrators, contractors, and trainees that at the end of October, I will be leaving my position as NIH Director to explore new opportunities and to devote much of my attention to writing.

I have said repeatedly that NIH is one of the true “wonders of the world.” For over six years, I have had the unparalleled privilege of leading one of the great institutions in history. Whenever an individual participates in a clinical trial or prevention effort, visits the doctor, stays in the hospital, has a medical test, or undergoes a procedure or treatment, they are benefiting from the extraordinary contribution you make to NIH’s single, great mission: improving the public’s health.

NIH has also been in the spotlight during a revolution in the biomedical sciences, one that continues to have broad and profound implications for academic institutions, industry, nonprofits, professional and scientific organizations, the health care profession, Government, and most important, for the health of the world. I am extremely fortunate to have led NIH during these unique times, which have brought with them complex challenges and amazing opportunities.

Your work will continue to transform the future of the agency and to play a key role in that revolution. Every day, people benefit from new treatments and potential cures for disabling and fatal conditions that result from your commitment and tireless dedication, even in the presence of complex problems and unprecedented challenges.

As recipients of NIH funding, you are among the world’s best, brightest, and most innovative scientists in a most competitive and challenging era for all of us. It is because of you and your contributions to science and health that NIH is known as the “crown jewel” agency of the federal government and you have every right to claim a stake in the agency’s success.
I also want to take this occasion to express my deep personal appreciation to the countless grantees who selflessly serve the NIH as volunteers on study sections, advisory councils and the many other activities the agency often calls upon you to join.

I know that my sentiments are shared by my colleagues at the NIH, and our gratitude runs deep. We are grateful for your support and the contributions you make every day.

Please feel free to distribute this message to your colleagues.

Sincerely,

Elias A. Zerhouni, M.D.

I'm not quite sure how I feel about this. I don't know that he did a fantastic job. He had some controversial moments. And I think he was largely behind the fiasco known as grants.gov ($2 billion spent on grants.gov and you can't buy a computer today that you can submit a grant with - no Mac OS, no Windows Vista).

Who wants to be an atom smasher?

It must be tough for your science to rely on a multibillion dollar machine the only works for a few days a year. Hard to make progress with such little instrument time.

Bad news for the world's largest atom smasher.

GENEVA, Switzerland (AP) -- The European nuclear research organization says repairs and the onset of winter will delay the startup of the world's largest particle collider until spring.

Chemical Boundary around the earth

They call it a "Chemical Equator. A 30-mile wide boundary separating the northern hemisphere's carbon monoxide pollution from the cleaner air in the southern hemisphere.

Here's more of the story.

It's Party Time

So, do you think this will encourage more kids to learn chemistry? I don't know but it is pretty cute.

Nature's Cowboys

Although I have never done research in the area, I have long been fascinated by molecular architecture that people create. Rotaxanes and catenanes have been targets for synthesis for many years. I often pondered whether this type of molecular assembly was purly synthetic or if there were natural analogs. All these years and I have never seen one from nature. Although, I should say, I have never searched for them. But I was quite astonished today when perusing the JACS ASAP articles to see this paper on the characterization of a lasso peptide. Finally confirmation that nature is indeed wiser than all of us and has probably already made anything that we can come up with. It's an interesting compound and makes me wonder why nature needs the lasso. Are there biological ranches with peptidic cowboys riding around? Does she use this to rope bacterial calves? I think I'll have to learn more.

Isolation and Structural Characterization of Capistruin, a Lasso Peptide Predicted from the Genome Sequence of Burkholderia thailandensis E264

Thomas A. Knappe, Uwe Linne, Séverine Zirah, Sylvie Rebuffat, Xiulan Xie, and Mohamed A. Marahiel

DOI: 10.1021/ja802966g

Better Living Through Chemistry

Greetings Blog Readers. I know there's at least two of you out there. Thanks for sticking with me. I've been away from civilization for 10 days. Yes, finally, a long-deserved vacation. I was in the wilderness. No cell phone signals. No internet. No pressing deadlines. Well, I have those more than ever now that I'm back, but for a while I could forget about them. It was absolutely wonderful. I realized when I was out there among the bears that every part of our lives is made possible because of chemistry. Sure, I can talk about how I couldn't get to such beautiful places without refined gasoline and automobiles, at least I couldn't get there quickly nor easily. I could talk about how I really needed my synthetic fabric tent to protect me from the elements. I could talk about how the old Coleman stove performed beautifully to provide me with bacon, eggs and the essential nutrient, coffee every morning using Coleman fuel. But I won't talk about those things. They are the obvious ways in which chemistry aids us in daily living. No, I want to talk about how chemistry makes our world absolutely fascinatingly beautiful. From billion year old granite cliffs to multicolored bacteria that live in scalding hot sulfur infused water. None of this would be possible without chemistry. And it is the sheer beauty of nature's chemistry that soothes the soul and makes me realize why I am really here on this planet. To make lives better. We can do that through chemistry.

Ok, I really am rambling. I had forgotten what a great vacation can do for one's perspective. Time to get back to the grindstone. Look for some organic chemistry soon!

Of Wine and Chemistry

I was away at a conference last week. One of those great small conferences where you can spend a lot of time interacting with people outside of the talks. It was great. I'm convinced the best science is discussed over beer and wine. I titled this blog post Wine and Chemistry because I like wine. It's not that I don't like beer. I do. I just can't drink very much of it before I feel bloated and uncomfortable. Thus I much prefer a nice red wine to drink while pondering the deeper aspects of asymmetric catalysis. I am not alone in this. Some friends of mine who were also at the conference are wine lovers and we had a nice little private wine tasting one evening. It was a wonderful experience as I got to taste a wine that was over 40 years old. The cork you see above is from that special bottle of Rioja. Although it was delicate and it broke when we pulled it from the bottle, it was in surprisingly good shape. The wine, on the other hand, was about 20 years past its prime. Not spoiled but it definitely was flat. It tasted like compost. That brings me to a little bit of chemistry. The wine was definitely oxidized but was not vinegar. It was stored well and the closure held up against the ravages of time. It was almost sherry like. Of course the one thing that distinguishes an oxidized wine like sherry is the presence of acetaldehyde. This had quite a bit of it. The tannins were completely gone. I wonder if there was any resveratrol left? Definitely not a wine I would pop and pour at a picnic but it was truly an experience to taste history.

Largazole and Histones

I have a certain affection for things that affect epigenetic regulation. Hence my interest in a class of enzymes called histone deacetylases (HDACs). These are zinc-dependent hydrolases that cleave the acetate group off of the lysine residues on the N-terminal tails of H3 histones. The bottom line is that deacetylation of these proteins that DNA wraps around turns off gene expression. In some cancers, tumor supressor genes are turned off and application of HDAC inhibitors turns them back on causing the cancer cell to die its normal death. That is a simplistic description. It is actually much more complicated than that. A simple animation of this is provided on the Methylgene web site.

In January, the Luesch group from Florida reported (J. Am. Chem. Soc., 130 (6), 1806 -1807, 2008. 10.1021/ja7110064) the isolation and characterization of an antiproliferative natural product called largazole. They subsequently synthesized it and discovered it was an inhibitor for HDACs (J. Am. Chem. Soc., 130 (26), 8455–8459, 2008. 10.1021/ja8013727). The synthesis is pretty efficient encompassing 8 steps with an overall yield of 19%. That's not too bad. Andy Phillips, in Colorado, has just published another 8 step synthesis and have confirmed the Leusch findings (Org. Lett., ASAP Article, 10.1021/ol8013478 ). In addition they have done some NMR conformational studies to show the solution structure of this interesting molecule.

What I find very interesting about this story is that the compound looks so very similar to cyclic peptide HDAC inhibitors developed in Japan (FK228, link to PDF). The sulfur gets buried into the active site pocket to bind the catalytic zinc while the cyclic structure binds to the surface of the enzyme. Both are necessary for the nanomolar level of inhibition of Class I HDACs that are observed for these compounds. Knowing the structure of FK228, I would have immediately made the connection between largazole's antiproliferative effects and HDAC inhibition. The original isolation paper does not speculate on that which makes me wonder if the Leusch group only made this connection later. I presume so.

The way this story has unfolded reminds me that I need to search more broadly when I am looking for HDAC inhibitor structures. Just searching on the keyword 'hdac inhibitor' is not enough and probably misses some compounds that people haven't yet connected to HDACs.

Atomic Noodles

Ok, I hear the voices from my last post and have decided to commit to trying to keep this blog going. My goal is to make sure I publish a post at least every week, if not more often. I've realized it doesn't have to be a chore and that I don't have to always have some latest greatest chemistry from the just uploaded ASAP's. I can do some fun stuff. I can even borrow from other stuff on the web. Why not? People do that all the time on their blogs.

Ok, then. How about a little bit of video? I know it's not directly chemistry, but it does fascinate me. From "The Ring of Truth: Atoms," here is Chef Kin Jin Mark pulling noodles.

To be or not to be

Oh, I know I've been ignoring this blog. I wondered if anyone even read it. It has dropped down on my list of priorities. But now I read over at Homebrew and Chemistry that my blog is being chopped from at least one person's reading list. I suppose I should have seen it coming. The question is, will this inspire me to reinvigorate Carbon Tet or should I let it die in quiet peace? Perhaps if people leave a comment or two it might help me make up my mind.