Young University of Queensland scientist Dr Peter Cassidy has invested six years of his life in building frameworks for new drugs.
"One way to think of our work is as Meccano?-like sets for drugs," he said.
The patented, platform technology in drug design develops new molecules with significant potential. It may unlock promising leads for new anti-cancer, obesity, and anti blood-clotting agents, among others.
The technology results from the work of Dr Cassidy and Professor Paul Alewood at UQ's Centre for Drug Design and Development, now part of the $105 million Institute for Molecular Bioscience (IMB). Professor Alewood is IMB Deputy Director.
But the project could falter if not for initiatives by the Government and the University to provide seed capital for promising new research with commercial potential.
"The project started off in an excellent environment at the 3D Centre, but once my PhD was completed I had to make a difficult decision - stick around and try to commercialise the work, or follow the standard overseas post-doc model. I'm still here but it's taken until now to get close to organising some funding.
"This situation is one example where an organisation like Uniseed can bridge the gap to stop things drying up."
(Uniseed Pty Ltd, Australia's first university-based venture capital fund, is a joint equity and management venture between Melbourne Enterprises International (MEI) and UniQuest Pty Ltd, the respective commercialisation arms of the Universities of Melbourne and Queensland. Launched in September with an initial $20 million capitalisation, it will invest in promising technologies, projects and ventures at their earliest stages).
Dr Cassidy needs to attract seed funding from venture capitalists impressed with the brilliance of the scientific approach and its commercial potential.
"The difficulty for many young scientists is that they can't attract grants or venture capital because they don't yet have a track record, and are not yet in a senior position. It is easy to see why many become part of the international brain drain. Salaries in the USA in my field are quite high," Dr Cassidy said.
"Competitors with similar technology working in the US have already spent US$35m developing a company. Although we can start small, if we are serious about industry development in Australia, we need to think of funding our good ideas on that sort of scale. It's a difficult situation.
"The question I've got to ask myself is whether it's worthwhile pursuing my project in Australia. In my case, it's now looking more worthwhile."
Dr Cassidy, a research officer at the IMB, said the patent protecting the technology was now currently in national phase filing. Six years of development work had been done, and proof of principle had been completed. The technology, known as peptide turn mimetics, was now ready for immediate application to new drug discovery at a number of targets.
The patent describes methods for making new compounds that imitate or mimic the important features of the "natural drugs" in the human body, for example peptide hormones and related compounds. The methods allow the transfer of the sidechain groups of the peptide (the key features for drug action) onto a new framework, resulting in a new (patent protected compound).
The peptide mimetics formed by this process are better potential drugs than the peptides due to lower molecular weight, increased stability, increased control of shape (and therefore selectivity) and more options for optimisation.
"It is a potentially highly efficient method for drug candidate generation," he said. "The technology creating molecules to fit receptors can be applied to heaps of different things. It's a method of gently clipping a couple of things together which allows us to build drug models with lots of things hanging off them.
"To use an analogy, you can make a key turn in any lock if you have the right lugs on the key. We can attach the right lugs."
Dr Cassidy said the idea of making peptide turn mimetics as an effective approach to drug development was first devised by an English drug designer (P.S. Farmer) 20 years agoand much work had been done on the idea since.
"Research over the past 20 years has demonstrated that it is very difficult to develop useful methods for the synthesis of turn mimetics, so with few effective methods this approach to drug development remains under exploited," he said.
"We have discovered some new chemistry that has enabled us to develop useful methods of mimetic synthesis. These methods are the best now available, and should enable efficient optimisation of lead compounds to active and selective drug candidates.
"The current boom in biochemistry and genomics is resulting in the discovery of an unprecedented number of new targets for drug development. Our platform technology is applicable to a significant proportion of these new targets giving large leverage to value if this drug design approach is shown to be effective and efficient."
Dr Cassidy said the project planned to produce a selection of the turn mimetics (about 100 compounds) directed at a range of receptors from the large group known as G-protein coupled seven-trans-membrane-domaine receptors (GCPRs).
"These receptors are ideally suited to the application of the peptide turn mimetics technology, and the probability of generating a number of significant lead compounds is high," he said. "Any lead compound produced could form the basis of a drug development program collaboration, or be sold or licensed."
Drugs for GCPRS are a large and important group of products. The GCPRS are the single largest group of receptors in the human genome, and play a central role in regulating the processes of all eucaryotic cells. There are already several hundred GCPR sequences known from the human genome project, most with unknown function.
He said they were proven effective therapeutic targets. It was estimated that more than 50 per cent of modern drugs were targeted at GCPRs, and 25 percent of the top 100 drugs (by sales) were GCPR ligands, with total sales of about US$16 billion in 1997.
Dr Cassidy, who undertook his undergraduate and PhD degrees at UQ, has received some financial support from Australian Postgraduate Research Awards, and from the IMB.
"I've also supported myself because I believe in what I am doing," he said.
ftp site for pic of Dr Cassidy with a model of a peptide mimetic: http://photos.cc.uq.edu.au/PNF:byName:/ScienceWriters/
Media: Further information, Dr Peter Cassidy, telephone 07 3365 1271 (work), 0408 733 220 (mobile), p.cassidy@imb.uq.edu.au or email: communications@mailbox.uq.edu.au
