Unnatural Amino Acid Synthesis

This summer, one of the projects I have been attempting to complete is the synthesis of a novel unnatural amino acid. Unnatural amino acids are those that contain an R group that is not found anywhere in nature–it must be synthesized in a lab setting. Unnatural amino acids are an extremely exciting field of study at the moment in biochemistry, because it allows us to create proteins that have new functionalities that we can take advantage of in a number of ways that are still being explored. One example of this would be the attachment of a fluorescent signal to a protein via an unnatural amino acid, such as in my ULP project I blogged earlier about.

This particular unnatural amino acid looks like a normal amino acid residue, except in the place of a hydroxyl group is a silicon atom surrounded by three methyl groups. Silicon has a number of properties that allow it to be extremely useful in select biochemical situations. The more unnatural amino acids we have access to, the more options we have when approaching a problem.

My project in synthesizing this particular amino acid has been quite long. As with any science, the reality is that sometimes things work once, and when you repeat it in what you think is the same way, it suddenly doesn’t. I have succeeded in the steps leading to the final product several times, but in the step called “deprotecting” in which extraneous carbon groups are removed, the silyl group has also come off. It is a difficult balance to achieve–you have to subject it to relatively violent conditions, but too violent and the chemical group that we care most about will also be damaged. We have approached this problem in a variety of ways, but none have been able to work outside of my first attempt, which we have not been able to replicate. There has been some success, however, as I have expressed protein with the unnatural amino acid, as one deprotection trial worked. We are now attempting to refine and repeat that process so that we will be able to reliably create this product for use in our lab.Screen Shot 2018-07-06 at 3.03.30 PM

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