We gotta get out of this place

On Monday morning the Nature offices in the King’s Cross area of London were evacuated.

The problem? – Gas.

Following a fire on a nearby building site, there was a danger that four gas cylinders would explode (BBC coverage here). The standard procedure apparently involves cooling down the cylinders with water and then waiting 24 hours before removing them. I remember last year when a similar thing happened in the back of a van on the M25, someone suggested deliberately blowing up the cylinder by firing an armour-piercing bullet at it – a much more instant, and obviously spectacular, solution! (Unsurprisingly, the authorities went for the watch-and-wait approach).

I worked in chemistry labs for quite a few years and never had trouble with gas cylinders – it seems ironic that only now they cause me problems…

Anyway, two days later, we’ve been allowed back in to our offices – without a single shot being fired.

Sometimes gas is not a laughing matter.

Stuart

Stuart Cantrill (Associate Editor, Nature Nanotechnology)

On the ball

For those of you not afflicted by World Cup fever, turn away now.

For the rest of us addicts, it’s finally here…

Despite England’s tepid performances we are through to the second round and now that Rooney’s back, we’re obviously going all the way to the final. Of course we are. Seriously. Come on now, stop laughing.

I’ve noticed that one or two chem blogs out there have also turned their attention to Germany 2006, including Paul at The Endless Frontier who is spurring on Team USA (who won’t be going to the final, or even the second round – sorry Paul). Also check out the special feature at nature.com.

Just how distracting/addictive/consuming is the World Cup?

A recent story reports that the World Cup may cost the British economy a staggering £4 billion in lost productivity – although not as many people may stay away from work as they did four years ago, the broadcast of the games live on the web by the BBC is likely to have a significant impact (I was going to put the link in here, but then I would feel partially responsible for that £4 billion – and of course, I have no idea what the link is and have no intention of going there…). Another study, however, claims that the influence of the World Cup may be just the opposite and that it may lead to increased motivation and foster greater team spirit.

This all reminded me of a review article published by K C Nicolaou back in 1996 concerning the total synthesis of brevetoxin B. In the final stages of the synthesis, there was an unexpected delay, which is best described in Nicolaou’s own words:

Projections were made that by the end of August 1994 we would reach our destination and submit the papers for publication early in September. I was convinced that these five men would carry out their mission as planned, for by then I was well aware of their talents and commitment. As it happened, one more August would come and go before we would arrive at “Ithaca”. In my calculations, I had neglected a small detail, a detail that became an important factor, and one that “Poseidon” would exploit at our expense and inflict one more delay before the final success…

During the summer of 1994, when the final campaign towards brevetoxin B was taking place, the World Cup in Soccer was hosted in the U. S., and all the members of the brevetoxin B team were either European or Japanese! Placing such soccer fanatics on the team for this highly demanding operation was rather unfortunate. Well, you can never think of everything in total synthesis! Brevetoxin B could not, however, escape for much longer, and before the end of the fall in that year it was destined to yield to the enthusiasm and pressure of these relentless professionals. Needless to say, this victory was to serve well as a consolation to each one of them for their countries’ not winning the World Cup!

So there you have it, World Cup fever may or may not be bad for business, but it certainly gets in the way of lab work. Now, which games are on today…

Stuart

Stuart Cantrill (Associate Editor, Nature Nanotechnology)

Bruce Merrifield

I’m sure many of you know that Bruce Merrifield passed away a few weeks ago. In today’s issue of Nature, Stephen Kent wrote an obituary describing Merrifield and his accomplishments.

If your institution subscribes to the ACS archives, you can download “”https://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1963/85/i14/pdf/ja00897a025.pdf">Solid Phase Peptide Synthesis. I. The Synthesis of a Tetrapeptide" (you should be able to download the first page for free). According to C&EN, this was the “fifth most cited paper in the journal’s 125-year history.”

You may also want to take a look at Gutte’s & Merrifield’s classic 1971 JACS paper, in which they reported the synthesis of ribonuclease A (124 amino acids long: this “required 369 chemical reactions and 11,931 steps of the automated peptide synthesis machine without any intermediate isolation steps.”)

Merrifield also wrote two reviews in Science (in 1965 and 1986) – they’re both pretty interesting reviews (and it’s amazing to see how much changed in those 21 years…)

Joshua

Joshua Finkelstein (Associate Editor, Nature)

Twisting the night away

In today’s issue of Nature, Tani & Stoltz reported the first chemical synthesis, isolation, and full characterization of 2-quinuclidonium tetrafluoroborate: at first glance, you might think that this molecule would be easy to synthesize, as it’s quite small. But the amide bond is highly twisted (it is an ‘anti-Bredt’ amide: it violates Bredt’s rule), which makes this molecule very susceptible to amide hydrolysis. Harry Wasserman wrote the accompanying News & Views article, in which he says:

Amides are surprisingly robust compared with structurally related derivatives, and it is believed that this linkage gains stability from electron ‘delocalization’ … In circumstances where such coplanarity cannot be achieved without distortion of the structure, as would be the case with 2-quinuclidone (Fig. 1b), stabilization of the amide bond by electron delocalization is inhibited. Such twisted amides demonstrate unusually reactive chemical behaviour compared with typical amide bonds.

He then continues:

In 1941, during his studies on the synthesis of quinine, the young Harvard investigator (and eventual Nobel prizewinner) Robert B. Woodward thought deeply about the reactivity expected of this type of distorted amide. As one of his first graduate students, I was given the problem of synthesizing 2-quinuclidone. Originally, this research was largely of academic interest, but a few years later the expected chemical behaviour of twisted amides became an important issue in the determination of the structure of penicillin.

Stoltz said that he first learned about this molecule when he was house-sitting for Wasserman during graduate school. A few years later, EJ Corey mentioned the molecule to Stoltz (who was doing post-doctoral research in Corey’s laboratory), calling it a “classic unsolved problem in synthesis.”

If you’re interested in learning more about this molecule, you can download the CIF file from the Cambridge Crystallographic Data Centre and take a closer look at this highly-strained amide bond…

Joshua

Joshua Finkelstein (Associate Editor, Nature)

You down with NNB? (Yeah you know me…)

Earlier today, the beta site of Nature Network Boston went ‘live’:

Nature Network Boston is the online meeting place for you and fellow Boston scientists to gather, talk and find out about the latest local scientific news and events … We believe that science benefits from local interactions and collaborations … [b]ut do you really know what that lab down the street is actually doing? Nature Network Boston will help you find that out. We aim to foster new ways for you to meet and get to know your neighbors.

The website has local (scientific) news, a list of events and scientific talks in the Boston area, and blogs from local scientists. It’s free to join NNB – though you’ll need to register to create your own personal profile page, post comments on the blogs, or form or join groups to network with other scientists. If you’re feeling creative, you can apply to write a blog yourself…

They’re going to add a number of new features in the coming months, so if you have any suggestions you can contact Corie Lok, the editor of the site…

Joshua

Joshua Finkelstein (Associate Editor, Nature)

OK Computer

Chemical & Engineering News published a brief news story today on Ashworth et al., which appeared in the June 1st issue of Nature. In that paper, the authors showed that computational protein design could be used to alter the specificity of the homing endonuclease I-MsoI. The redesigned enzyme was highly active and it cleaved the new recognition sequence about 10,000 times more effectively (in vitro) than the wild-type enzyme.

Earlier this year, David Liu’s laboratory demonstrated that it was possible to use directed evolution to modify the specificity of another homing endonuclease (I-SceI), but Ashworth et al. is the first paper in which computational protein design was successfully used to modify the specificity of a homing endonuclease.

The authors say that “the method should be generalizable to any protein–DNA interface redesign problem: for example, the reprogramming of transcription factor binding specificity” and they believe that “[t]he use and refinement of the computational modelling and design strategies described here should … [enable them to design] novel proteins [that are] able to recognize and cleave any desired DNA site with high specificity for targeted genomics applications.”

Joshua

Joshua Finkelstein (Associate Editor, Nature)

It’s all about the Benjamins

I thought some of you might want to know about a new source of funding for scientists who plan on attending a Gordon Research Conference in 2006:

The Nature Publishing Group (NPG) supports the broadest possible participation of qualified scientists in scientific conferences. To forward this goal NPG has established the NPG Awards to help assuage one of the factors that prevents conferees from various countries with developing economies from attending the renowned Gordon Research Conferences. NPG has provided limited funds for individuals from developing nations to attend Gordon Research Conferences in 2006. Applicants from all nations/regions are eligible, except those nations/regions listed below. [click here to see the list of non-eligible countries]

You need to be accepted to a 2006 GRC in order to apply for funding, and you could get up to $1,500…

Joshua

Joshua Finkelstein (Associate Editor, Nature)

Summertime

It’s about 85 degrees in Boston and I got a sunburn walking into work – this means that the summer is officially here. OK – I know the first day of summer is still a few weeks away, but the sun is shining and it’s time for me to start thinking about summer conferences.

If you say the words ‘summer conference’ to a group of scientists, I bet many of them think of the Gordon Research Conferences: you are whisked away with 100-150 other scientists to hear about exciting (and often unpublished) research for several days. Many of these conferences are in high schools or small colleges in New England, but don’t let the Spartan accommodations or the cafeteria food deter you from coming – I’ve only been to a few GRCs, but I’ve had a fantastic time at every one…

This summer I’m 99% sure I’ll be attending the Natural Products GRC and the Bioorganic GRC – I’d love to go to the Enzymes, Coenzymes & Metabolic Pathways GRC and the Organometallic GRC, but I’d be out of the office for the month of July, and I don’t think our authors (or my wife) would really like it if I was gone that long. Maybe next year the conference organizers will spread them out a bit…

Other summer conferences that look good include the RSC Organocatalysis conference (in early July), EuroBIC (also in early July), and the annual Protein Society meeting (in early August).

What conferences are you going to this summer? We’re always interested in hearing about exciting conferences, so if you’ve been to that conference in previous years, why do you like it? What keeps you coming back? (And please feel free to shamelessly promote a conference you’re organizing…)

If you’re at any of these conferences, keep an eye out for me – maybe we can chat about your research over a pint or two…

Joshua

Joshua Finkelstein (Associate Editor, Nature)