They have identified and produced the key enzyme that can turn small proteins known as linear peptides into more robust, chemically stable circular ones – making the peptides a leading candidate for future pharmaceutical drug design.
It was published today in the prestigious international journal Nature Communications – the team’s first breakthrough since gaining a million dollar Ramaciotti Biomedical Research Award in October to help develop technologies for more potent and affordable next-generation medicines.
Unique drug scaffold
Circular peptides are a class of proteins exceptionally resistant to chemicals, enzymes and heat because of their unique structural scaffold.
Dr Harris said they were less likely to be broken down by gastric acids than linear peptides currently in use, and can react more specifically with target molecules with fewer side effects.
‘Our enzyme comes from the original African plant in which the first circular peptides were discovered more than 40 years ago. That plant was used by women in the Congo in tea to accelerate childbirth.’
Dr Harris said it was the first time that the crucial cyclising enzyme from this plant had been produced in bacteria and used to make circular peptides in the laboratory.
Large volume yield
Professor Anderson said other people had synthesised circular peptides using sophisticated chemical methods.
‘But that’s an expensive process with low yields. The discovery of the cyclising enzyme will enable us for the first time to make enough of this circular peptide for clinical trials. We expect clinical trials will be about five years away.’
Some early applications, Professor Anderson said, could be for cancer and obesity drugs as well as for the treatment of pain.
‘For example, our colleague David Craik from the University of Queensland has already produced circular peptides that are hundred times more effective than morphine at relieving pain.
‘But until now it has not been possible to produce these peptides in the quantities required for clinical trials. We are hoping this work will make the dream of producing new generation pharmaceuticals a reality.’
So if you thought Uber was disruptive technology for taxi companies, Dr Harris and Professor Anderson have a gleam in their eyes for the pharmaceutical industry.
Their idea is to not only manufacture drugs in plants, but that one day you’ll be able to consume them straight from your potatoes, lettuce, tomatoes or rice. Now that could be a solution to spiralling health costs.
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Image: Dr Karen Harris at work in her lab.