Do not turn off your brains

I am back from my travel, although only for 2 days. China is calling me now and I will be on my way to Shanghai on Saturday to attend a conference organized by Professor Shengming Ma. This change of scientific scenery is interesting and therapeutic as I am getting used to being involved in completely different communities of scientists. While earlier this week I heard about a lot of new developments in the area of peptides and other biomolecules, I will now listen to some metal catalysis talks at Shengming’s gathering.

Tonight I just wanted to mention a story that we discussed with Steve Kent over some glasses of wine in Montpellier. If you recall, Steve is well known for his contributions to the development of native chemical ligation (http://en.wikipedia.org/wiki/Native_chemical_ligation) – a method for linking linear peptide precursors into longer chains, ultimately leading to proteins. This approach to the total synthesis of proteins has enabled some wonderful advances and is particularly meaningful if a target protein is difficult to express. But let’s set aside all of these targets and concentrate on shorter peptide precursors that serve as starting materials to ligation. These peptides are still pretty long and someone has to make them using peptide synthesis. It was comforting to hear how, over a glass of Cabernet, Steve bashed automated peptide synthesizers. As it turns out, manual synthesis is his preferred (bar none) approach to making proteins, to the extent that even a molecule as complex as EPO was made in his lab using this approach back in 2012. Here is a link to the paper detailing this feat:

http://onlinelibrary.wiley.com/doi/10.1002/anie.201106060/abstract

According to Steve, over-reliance on automated synthesis is really dangerous, which I agree with wholeheartedly. It is really cool that a lab that is dedicated to protein synthesis using shorter fragments does not rely on any automation. Next time my students try to convince me that they cannot live without automated peptide synthesis, I will tell them what Steve said: “There is a tendency to turn off your brain and get into all sorts of trouble once you hit that switch on the synthesizer”. Coming from someone who was trained by Bruce Merrifield a long time ago, this is worth listening to.

2 thoughts on “Do not turn off your brains

  1. when you make peptides on solid phase manually, you can do fewer couplings per day but you can see incomplete couplings right away by sampling and staining the resin.

    By the way, are you using chloranil test for secondary aminoacids? The modern version of the test (2% chloranil in DMF, with 2% acetaldehyde at R.T.) is from me…

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