Where in the world?

Well, I'm off on vacation for the next two weeks! As my better half lives in Germany, we don't get to see each other as often as we would like--we saw each other last at Christmas. This time we are going to meet "halfway." Technically, it is closer for him, but I'll take a 5 hour flight (from the east coast of the US) over a 10 hour flight any time. If there is internet access available, I will be posting updates from time to time. Otherwise expect to see pictures when I get back :o)

DNA detection

Picture taken from Hammond, D.M., Manetto, A., Gierlich, J., Azov, V.A., Gramlich, P.M.E., Burley, G.A., Maul, M., Carell, T. Angew. Chem. Int. Ed. 2007, 46, 4184. 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

In my mind, the future of cancer therapy is in the hands of personalized medicine; as the genetic makeup of each patient is different, it only makes sense to utilize customized therapies depending on the mutation affecting the individual. (Just look at the story of Iressa, and how well it works for Asian nonsmoking women with mutations in the EGFR tyrosine kinase domain). While the idea is a great one, personalized therapy is not a reality yet. Currently treatment options are too limited and often unspecific; methods to detect various disease markers are lacking. Personalized medicine depends upon the detection of minute amounts of DNA as well as isolation of particular genes from biological samples of interest, and the Carell group has developed a method to help with this.

Typically PCR is used for standard DNA amplification, although newer, more sophisticated techniques have allowed for detection of DNA down to the zeptomolar 10^-21 level. (I'd never even heard of that one, my super-geeky husband had to fill me in). Unfortunately, such methods require the use of expensive/complex technology, so Carell and coworkers have developed a simple method of DNA detection based on standard black and white photography techniques. First, a pinacyanol dye was modified to contain an azide functionality, and several alkyne-containing oligodeoxyribonucleotides (ODNs) were synthesized. After a copper catalyzed Huisgen cycloaddition, various concentrations of modified ODNs were spotted down on commercial photopaper, irradiated, and developed according to known methods (standard photographic darkroom setup). This simple procedure allows for the detection of ~300 attomoles (10^-18) of DNA!

Blogging Scientists...

Earlier today the paper fairy left the most recent Cell on my desk, open to the page "Scientists Enter the Blogosphere." Actually it was left on my chair, as my desk is currently a mess of papers (it's called writing a review), and I might not have seen it otherwise. There are a few people in my lab (including my boss) to whom I have casually mentioned my blog, but I'm pretty unsure if they have ever looked for it on the web. So it made me feel pretty good that my boss remembered I am a blogger.
Some fast facts from the article: Of 50 million blogs that exist, 4% of them deal with technology issues on a regular basis (20,000 of them are labeled as "science" blogs, although the term science is used loosely), 8% of internet users in the US write a blog, and only about 1000 of the science blogs out there are actually considered "authoritative."
I've been reading one of the featured blogs, In the Pipeline, for quite some time, and was thrilled when I was recently added to his blogroll. Some of the other blogs mentioned in the article that I found particularly interesting: Aetiology, The Daily Transcript, Sandwalk, and Useful Chemistry.
On a slightly related note, this recent post by Excimer (and all of the commenters there, especially Chembark) really got me thinking--Do blogs already serve as an unofficial review/comment system for scientific articles?

Going Decaf...

Several months ago, Justin P. Gallivan gave quite an entertaining seminar for the chemical biology department. While I'm officially a member of the organic division, I really enjoy the biological side of things, so I try to attend these seminars as often as possible (or sometimes I attend them when my boss sends out an email "please attend," which really means "required seminar"). If I remember correctly, Prof. Gallivan did a little "bacteria dance," and if a speaker goes that far to get our attention, he has my respect :o) His lab actually has done some extremely interesting work, and I've been waiting for a publication to come out ever since that seminar.

Last week, the article "Guiding Bacteria with Small Molecules and RNA" finally appeared in JACS. E. coli have 5 chemoreceptor proteins and thus can maneuver their way through complex chemical environments. While they naturally perform chemotaxis toward 30+ compounds, it would be useful in terms of bio-nanotechnology to reprogram these bacteria to respond to new and unique chemical signals. The pathway responsible for converting chemical ligand binding into a change in direction of the bacteria consists of 6 chemotaxis proteins, with the protein known as CheZ ultimately responsible for bacterial motility. With this in mind, Shana Topp from the Gallivan group created a theophylline-sensitive synthetic riboswitch to control translation of CheZ; without theophylline, the conformation of mRNA prevents translation of CheZ, forcing the bacteria to tumble in place. Once theophylline is added to the mixture, the mRNA adapts a different conformation in which the ribosome binding site is open, which allows for expression of CheZ and forward movement of the bacterial cells. Caffeine, which has a structure similar to that of theophylline, did not elicit a response from bacteria, indicating that the observed changes in bacterial motiliy are dependent on the riboswitch. As Topp and Gallivan jokingly state, "E. coli pick decaf!"

Nucleophilicities of Amines in Water

picture taken from Brotzel, F., Chu, Y.C., Mayr, H. J. Org. Chem. 2007 72, 3679-3688. Copyright 2007 American Chemical Society

A lab-mate alerted me to this article in the current issue of JOC, and if you are at all interested in comparing the nucleophilicities of amines, then it is worth taking a look. In the past, nucleophilicity has been measured by investigating the kinetics of nucleophilic additions and substitutions. For instance, the rate of reaction of primary or secondary amines with CH₃I/CH₃Br or stabilized carbocations can be measured and directly related to nucloephilicity using a general formula:Bunting [1, 2] and coworkers have characterized the nucleophilicities of over 70 amines to date using a variation of this method (reactivity towards 1-methyl-4-vinylpyridinium cation as well as methyl 4-nitrobenzenesulfonate).

More recently, researchers from the Mayr lab have utilized benzhydrylium ions (electrophiles) to study the nucleophilicity of various non-amine nucleophiles; as it would be useful to have methods for comparing nitrogen bases in order to design new organocatalytic reactions, they have expanded these methods to include 26 amines. While many of the observations are completely logical (increased branching decreases the nucleophilicity of primary amines, ammonia is less nucleophilic than methyl amine which is less nucleophilic than dimethylamine--which tracks nicely with basicity), others were quite unexpected (at least for me, and I'm certainly not an expert). According to this research, aniline, which is quite a bit less basic than ammonia, is a much stronger nucleophile than ammonia.

As chemists, we all know that basicity certainly doesn't equal nucleophilicity, but this article really drives that fact home.

Update: Thanks to Handles for pointing out this website where Mayr has put all of the nucleophilicity data online :o)

Random observation

Why does it disturb me so much that chemistry.com is not a chemistry website at all, but an online dating community? That is just wrong.

Aliens

Well, this last week has been a hard one--Fortunately I'm far enough along in my graduate career that I don't have to deal with the stress of final exams, but my body decided to play tricks on me anyway. After dealing with the stomach flu last week, this week I've been suffering from a head/neckache. Since I'd had it for over 5 days, I decided to go to the student health center, which was a big mistake--for some reason, they thought I had meningitis (Normally I would put a wikipedia link there, but the picture that came up when I did that made me sick to my stomach, so today I'll leave the link out), and they sent me to the emergency room. The doctors there assured me that I was only suffering from a muscle spasm in my neck, gave me some pain killers, and left me with a hefty bill to pay. When they can't tell the difference between muscular pain and a deadly illness, I start to doubt the effectiveness of the university health care system....So that explains why my post today will be relatively light :o)

If you're like me, when you think of aliens, you think of little green men with saucer shaped eyes and strange metallic clothing. Why do we always imagine aliens to be green--Is this really an accurate representation of animals or plants in other solar systems? Well after a lengthy review of photosynthesis on Earth, researchers at Rice University, Washington University, UIUC, and NASA have come up with a set of rules for predicting what colors might be photosynthetically relevant on other planets. Photosynthetic pigments evolve over time in sync with the atmosphere of a planet and the characteristics of its parent star; it is proposed that they have peak absorbance at the blue and red ends of the atmospheric transmittance window for light harvesting, as well as at the wavelength of peak incident photon flux. Thus, if we know the patterns of incident radiation for other stars, we can begin to predict what kind of photosynthetic machinery might be necessary on those planets, as well as the color of these photosynthetic pigments. So we can basically predict what color the trees might be on Jupiter.

Cool, huh?

I first read about these articles on heise.de, but a nice summary can also be found here on the Goddard Institute for Space Studies (part of NASA) website, with reprints of the two Astrobiology papers here and here.