Over the last 60 years, drugs have been made more potent and more bio-available by subtle chemical modifications. The substitution of other functional groups such as fluorine has resulted in drugs such as fluconazole, an anti–fungal; fluticasone, an anti–inflammatory steroid; flucloxacillin, an antibiotic; and fluoxetine, an antidepressant.
However, in the field of protein-based drugs such as insulin and antibody therapies, the ability to produce more potent ‘biologics’ through functionalised proteins has yet to be realised. Such substitutions could, for example, allow the development of a skin cream to administer insulin, or drugs which efficiently target and destroy cancer cells. The principal problem in creating such ‘unnatural proteins’ is that they are synthesised using the natural building blocks of 20 amino acids in living cells.
Martin Chalfie, Osamu Shimomura, and Roger Y. Tsien were awarded the Nobel Prize in Chemistry in 2008 for their discovery and development of Green Fluorescent Protein (GFP). One of the most important tools used in contemporary bioscience, GFP has enabled researchers to develop ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread.
An unnatural version of GFP was pioneered by Dr. Farid Khan of Protein Technologies. ‘Kryptonite’ GFP contained fluorine atoms not found in nature. Spectacularly, the resulting GFP was at least ten times brighter than the natural form of GFP!
The fluorescent chromophore inside the structure of Kryptonite GFP contained fluorine atoms which enabled the electronic configuration of the protein to fluoresce even brighter. As far as we know, this is the largest amount of unnatural protein produced to date. This opens up the real possibility to design future biologics as ‘Super Drugs’ with a plethora of new substitutions to produce potent drugs that were not thought possible.
See Dr. Farid Khan, inventor of the technology, demonstrate the ‘GFP Kryptonite Bioreactor’ at GIANT.