On protein synthesis, ligation, and expression…

Some of you know me – I love ligation technologies. As a chemist, it is exciting that synthesis can deliver a protein. Cool stuff. Now… Here comes a question I would not have asked had I not tried protein expression myself. In one of our recent experiments, Elena and I got about half a gram of a particular protein (more on that in the future) from E.coli in about 3 days. This technology is really unbeatable when it works. You don’t need to worry about epimerization (the way we do when ligations are considered), folding, etc. I am just curious – out of scientific publications that describe protein synthesis using modern chemical ligation methods, how many actually describe syntheses that CANNOT be performed using expression methods? Because — I tell you what (having done this myself) — you just cannot beat expression. OK, I understand that not all proteins express well and this is a good argument… But still – are you telling me that whenever people publish a chemical synthesis of a protein type of paper, they preamble their work by saying that this synthesis CANNOT be achieved using expression methods? If such synthesis can be done using expression, I honestly just do not see why you would use any method other than expression…

P.S. You want post-translationally modified proteins? Use insect or mammalian expression. From what I saw, folks at SGC do that routinely…

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