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You know what’s even better than the GRE?

The Chemistry GRE!

I had the opportunity (read:  obligation) to take this test recently, and unlike many, I found I had a really great time.  For those who have yet to take it, the Chem GRE is a 3 hour long test where you are asked a variety of questions on all branches of chemistry, with the major focuses on Organic and Physical, with some inorganic, transition-metal, and analytical chem thrown in for good measure.  In case you thought you read that wrong, you didn’t.  The test is, in fact, three hours long.  It is a very long three hours, and can be intimidating. Here are some tips and tricks to being successful on the GRE:

First, concentrate on the stuff you don’t know.  Unless you finished all of your chemistry classes by the end of junior year (unlikely?), you probably won’t know some of the concepts outlined on the GRE.  Pick up a review book and at least familiarize yourself with some of the basic concepts.  For example, I had no idea what the 18-electron rule was for metal complexes before taking the GRE. It’s a startlingly easy concept to learn, and will earn you a couple easy points.

Second, take a day or two and review the stuff you haven’t looked at in a while.  For me, that was P-Chem.  A GRE book will help with this.  Just remember that the GRE sometimes will go into absurdly small detail on some material you learned in sophomore year, so just stay on top of your chemistry knowledge.  You’ll be surprised with how much you remember.

Third, remember to get some sleep.  My test started at 8:30, which meant I had to leave the house at 7:45.  I’m not really used to waking up that early, so it was really no fun.  I’m sure all of you have taken enough standardized exams to know this, but just reminding you.  Also, eat breakfast and get hydrated before the exam.  It’s around 3 hours long and the exam proctors will not let you drink or eat anything while you’re taking it.

Lastly, and anecdote.  This summer I started lifting weights with a friend of mine as a way to stay in shape (and secretly to be able to carry those 20 gal jugs of DMF around the lab and not hurt myself).  He is an economics/philosophy major who is also a varsity swimmer, and has a lot of really interesting things to say about life.  His philosophy on exams is this:  treat it like a game!  You win the game if you get the most points, and you’re playing against everyone else in the room.  Games are fun.  Therefore, treat the test as a game, and you’ll have a blast.  I took this philosophy in with me, and really enjoyed all the really tough questions – they’re just chemistry, right?

Yup, still in Kansas.

A mitotic kinase - oncoprotein!

Your protein of the day! Aurora A Kinase is protein involved in mitosis, and is generally upregulated in cancerous tumors. It is very difficult to target because of its highly conserved C-terminal Kinase domain. (See inset for ADP) From PDB: 4mq1

Wow!  It has certainly been a long time.  I guess a blog can sometimes be like a google reader account.  You can get into the rhythm and read all your articles for a week, but then you forget about it and you get 620 items into your unread folder.  Oops.  Anyhow, here’s just a little post to get y’all updated with what’s going on with me.

Senior year is going pretty well  - I’ve been spending 20-30 hours in lab a week.  I would like to be spending more, but I have these silly things called requirements to fulfill.  Oh well, I guess my 45-50 hours weeks can wait until I start graduate school.  Research is definitely on a better rhythm than it has been in the past.  I feel like I’ve stopped making some of the small mistakes, and can now actually execute the science at a high level, and pretty efficiently.  My only limit now is how much time I have (and how quickly I can get reagents mailed in).  I’m sure once I start working in cells or doing some more serious organic chemistry my pace will bog down a bit, but for now it’s pretty nice to be working efficiently.

I’ve started work on a thesis, which is going on nicely so far.  Unfortunately, keeping procrastination to a minimum is harder than I anticipated.  The plan right now is to really start working on the methods, and hopefully be up to date by winter break (when I really) have to start writing.

As for the blog, you’ll get in the near future my ruminations on the Chem GRE, some more talk of Chemical Biology, and a little bit on the application process, or what little of it I’ve gone though.  Stick around for a whole lot more content in the coming weeks!


What is chemical biology? Native Chemical Ligation!

Disclaimer: I am not an expert. In fact, this series of blog posts is as informative  to me as it is to you. Probably even more so. My views and the views of people interviewed for this blog do not, in fact, reflect what exactly “chemical biology” is, but only a snapshot.  Please direct any comments or suggestions below!

The two subunits were synthesized separately

HIV-1 Protease, one of the first proteins synthesized via chemical ligation (PDB 3CDR)

On the last “What is Chemical Biology” post, several readers had comments that Chemical Biology was nothing more than a relabeled version of Pharmacology.  To be honest, they do have a point.  A lot of Chemical Biology that I have investigated so far has been drug discovery, which falls squarely in the realm of Pharmacology.  To that end, I have decided to find something that fits in this field that is more “pure science.”  Enter Native Chemical Ligation.

Native Chemical Ligation was born of the effort of the total synthesis of proteins.  Solid phase peptide synthesis (SPPS), as most of you probably know, is limited to around 50 residues as the peptide begins to form secondary/tertiary structure around  the resin bead it is attached to.  This secondary structure could reduce the (already not so great) efficiency of the coupling reactions.  In addition, by this point in a peptide synthesis, the overall yield is very low as well.  This results in some very major problems in the total synthesis of proteins.  How did bio-organic chemists solve this problem?  You can probably guess the answer by now.

Native Chemical ligation is born from Chemical Ligation, a method to connect two synthesized peptides together without the use of protecting groups on each and every side chain.  Chemical ligation used chemistries involving the formation of thioester or thioether bonds among other linkages.  While Chemical ligation resulted in the total synthesis of several peptides, there are several disadvantages to this technique, including the replacement of a nitrogen with a sulfur atom.  This is the equivalent of placing a soccer ball in the place of a tennis ball.  Naturally, this can result in problems in protein folding.  Native Chemical Ligation is a method by which a native peptide bond can be “installed” into a synthetic peptide structure.

Look!  Modification!

Native Chemical Ligation Mechanism (Credit: American Physiological Society)

The chemistry is surprisingly simple.  A S to N acetyl transfer upon ligation of the two peptide fragments results in a native peptide bond and an easily purified thioester side product.  This reaction is shown in the figure.  Native chemical ligation can also be used to synthesize glycerolized peptides at specific sites.  This was described in an article out of Nature.  Overall, a pretty cool mechanism for synthesizing whole proteins, and making slight alternations without using recombinational techniques.

Yale Student Dies in Chemistry Machine Shop

After standing for some time in the rainy streets of Boston, I finally hailed a cab to the airport. As I tried my best to wring myself out, while not making a mess of the cab, the cabbie chattered away into his bluetooth, and the radio was on some news station, barely audible.

My ears perked up when I heard “…chemistry…”. I leaned a bit closer to the speakers.

“…Yale student died…”

“Hey, can you turn this up!?,” I blurted to the cabbie.
“Huh?,” he replied.
“The radio – can you turn it up?”
“Oh, ok,” he said, turning the radio up as the news report ended.

While we sat, listening to the weather and traffic at an uncomfortably loud volume, I hopped on my space-phone to get the full scoop.

Last night, Yale senior Michele Dufault died in an accident in the Sterling Chemistry Lab. Details are unfortunately spotty, and for now, the only chemistry-related news is that the accident occurred in the machine shop, but word on what exactly happened. The full story can be found at the Yale Daily News, and I’ll post updates here as they’re available.

She was an astronomy and physics major, and by all reports, generally awesome. My deepest sympathy to her family, and the Yale community.
Stay safe out there.