Automated Peptide Synthesis
Bruce Merrifield Invented a New Method for Bulk Protein Synthesis
The discovery in 1963 by Bruce Merrifield of a way to automatically synthesise polypeptides and protiens accurately and without loss of yield.
During the twentieth century, scientific advances have been made in various different ways. Sometimes it has been through the hard slog of painstaking research, sometimes pure luck has played a large part. Some discoveries have been made by scientists looking to save time and make life easier for themselves!
A New Method
Robert Bruce Merrifield was a young biochemist at the Rockefeller University in the US who was attempting to synthesise polypeptides by the usual methods. These methods involved slow procedures of recrystallisation and purification which needed great skill and reduced yields each time they were done. Merrifield's problem was that due to his inexperience it took a long time and his yields were very low. He began to think that there must be an easier way.
Polypeptides
Polypeptides are long chain molecules in which lots of molecules called amino acids are joined by “peptide bridges”. These molecules are important in nature where they go by the name “proteins”. These proteins are used in many different bodily processes. They are enzymes which cause important reactions to happen in the right place at the right time. They are also used for transport, as in haemoglobin, used to transport oxygen in the blood. They are also used in cell structure and many other natural processes.
1963 Paper
Merrifield published a paper in 1963 in which he outlined a completely new method which was simpler and easier than the accepted methods, and also had the potential to be automated. The idea of automation was considered far-fetched at first by the establishment, but it was soon found to be perfectly viable and is used to this day to synthesise polypeptides and proteins.
Anchored
The method was based on using a solid polymer which was not soluble in any of the solvents to be used. An amino acid was then covalently attached to a bead of this polymer. Other amino acids were then added to the growing molecule, one by one until the required polypeptide was reached. This was then detached from the bead.
Simple Purification
The beauty of this method was in the way the compound was purified after each step. In the traditional methods a drawn out process called recrystallisation was used. This had the effect of reducing yields. The new method simply required washing with solvent, the bead with growing molecule then being simply isolated by ordinary filtration.
Further applications
The method has since been refined and used for many other applications. The mass production of important molecules like insulin has been made possible by this method. It is also used, not just to synthesise bio-polymers, but also many other complex natural chemicals which would have been impossible to synthesise by the previous methods.
