Elephants rarely get cancer: less than 5% of captive elephants die of cancer, compared to 20% of humans. Elephant genomes have at least 20 copies of the tumour suppressor, p53, which may explain their low cancer rates relative to humans, who have only one copy.
One of the things that is challenging about scientific research is that the problems needing to be solved are constantly evolving. Solutions which were previously considered to be adequate may become inadequate due to changing priorities, meaning that they need to be readdressed.
One such issue which I have become interested in is making peptides.
Peptides are long chains made by joining amino acids residues by amide bonds. Peptides, and proteins (which is the name used for long peptides) are vital components of many of the processes of life, and in recent years there has been ever increasing interest in the use of peptides as potential for treatments for a wide range of diseases. In 1984 R. B. Merrifield was awarded the Nobel Prize for his excellent work developing a technique to make peptides known as "Solid Phase Peptide Synthesis" or SPPS. The discovery of SPPS revolutionized peptide synthesis, enabling scientists to routinely make increasingly complex peptides, and is to this day the most commonly used method for peptide synthesis. However, SPPS requires large excesses of both the amino acids you are joining together and the chemicals used to form the linkage. As the earth's resources become increasingly depleted this waste becomes less and less acceptable, meaning that new ways to make peptides must be developed. In order to do this, we as scientists need to be as creative and innovative as possible to come up with new solutions for old problems. One potential solution to the challenge of peptide synthesis is the emerging field of flow chemistry. In flow chemistry, machines are assembled which use pumps to pump streams of reagents through thin tubing. By doing things like meeting two streams containing different reagents together, heating or shining light on the tubing, or flowing the reaction stream through a bed of solid reagents we can effect reactions with very fine control, which has been shown to be very beneficial.
My initial work in this area focused on making a type of naturally occurring molecules known as cyclooligomeric depsipeptides.
These molecules have repeating dipeptidol units derived from amino acids which are cyclized around to form a ring and have been seen to have interesting bioactivity. By using flow chemistry we able to make these molecules with significantly less effort, as one set up of the machines could be used to make all the amide bonds in the molecule with only minor revision to form the final ring closures. Additionally, we were able to significantly improve the yields for these reactions when compared to previous syntheses. As well as making three natural products (beauvericin, bassinolide and enniatin C) we were able to make three related compounds which have never been made before. This family of molecules can now be tested to see if they have any interesting bioactivity.
There is a way to go until we will know if flow chemistry can augment or even replace the current methods for commercial peptide synthesis, but this work definitely supports the idea that readdressing problems from the past can lead to improvements for our future.
Dr Zoe E. Wilson
Academic Fellow in Organic Chemistry
To read more about our synthesis of the cyclooligomeric depsipeptides see:
Daniel Lücke, Toryn Dalton, Steven V. Ley and Zoe E. Wilson*, “Synthesis of natural and unnatural cyclooligomeric depsipeptides enabled by flow chemistry”, Chem. Eur. J., 2016, 22 (12), 4206 – 4217. DOI: 10.1002/chem.201504457
"I recently presented my research at the ACS Fall Meeting in Philadelphia, Pennsylvania, USA. For this I recorded a 3 minute summary talk with the ASC Scientific video lab where I discuss this research in more detail."