Little Helpers

Mimotopes

Peptides are very much in the news at the moment. The recent furore over drugs in sport – fuelled by the investigations by ASADA into a leading footy club – has propelled peptides into the public’s focus and possibly given the impression that bodybuilding or slimming are the only uses for these fascinating chemical structures.

That is most certainly not the case, and it really is a pity the public doesn’t know more about peptides, especially since the world leader in the field, and the company that did more than anyone to stimulate the whole field of peptide and related chemistry research, is based right here in Australia.

Mimotopes Pty Ltd, with its headquarters in the Melbourne suburb of Clayton, harnessed the pioneering work of Professor Mario Geysen, who enabled the parallel synthesis of peptides and subsequently small molecules to become mainstream.

That was 25 years ago, and Mimotopes has since become a global industry leader in the peptide and discovery chemistry sector. The company develops, markets and distributes sophisticated biochemical products and services for the biotechnology and pharmaceutical industries, with clients including all the major ‘big pharma’ names and brands.

Mimotopes’ Managing Director Sonja Plompen agrees that until recently, very little was known by the general public about peptides and how they could be beneficial in medicine and related fields. Peptides were a known class of chemicals in science itself, but they are already present in the human body and were for many decades not seen to have much use in therapeutical terms. They are constituent parts of proteins, which in turn are digested in the human stomach and broken down, so it was generally thought they would not be retained long enough in the bloodstream to be of medical use.

Dr Geysen had been engaged within the respected research organisation Commonwealth Serum Laboratories (CSL) to investigate some aspects of foot-and-mouth disease in Indonesia and try to develop a vaccine against the disease. Almost incidentally, because he was searching for a particular method of producing the vaccine, he hit upon the means to (in the simplest of terms) ‘grow’ peptides, a method which Mimotopes (spun off from CSL in 1989) patented and which gave the company a lead it has never relinquished.

Mimotopes became the first organisation in the world to use ‘combinatorial chemistry’ – a process in which many thousands (and perhaps even millions) of chemical compounds can be prepared using a single process. One way to do this is the co-called ‘split-and-mix’ technique whereby you start with a large volume of a substance, halve it and add a compound, halve it again and add a second compound, halve it and add a third, and so on – almost ad infinitum. The result is what is known as a ‘library’ of compounds, chemicals stored for use in an increasingly wide variety of industrial and biomedical processes.

The ability to make lots of peptides quickly meant that they could be more useful and suddenly, says Sonja, “there was a big increase in demand for peptides. We had worked out a way of effectively commoditising them. Nowadays there are peptide synthesisers in almost every lab in the world.” Customers come from the academic and research sector, or big pharmaceutical groups, or small biotech outfits making designer drugs (ie by computer- designing a peptide and then examining ways of modifying it to produce a specific effect and to work for longer within the human body).

Peptide libraries are synthesised on Mimotopes’ unique “PepSets™” proprietary synthesis platform. Typically they are supplied at the 1 to 3 mg scale for fast, efficient screening work. In 2009, the company launched the peptide industry’s first fully-HPLC purified peptide library platform. Mimotopes’ proprietary process transforms unpurified ‘crude’ peptide libraries into fully purified peptides that have all been prepared to minimum 70, 80, 90 or 95 per cent purity by reverse-phase HPLC.

This library platform is readily accessible online and enables chemists, pharmacologists, cosmetics companies and many other companies in agricultural and bioengineering fields to ‘dial in’ a range of proteins that they can then test against a specific chemical (it could be a blood sample from a patient with a particular cancer, for example) and find out with amazing precision which compound will be the most effective.

Indeed, the Mimotopes website is a highly attractive and easily used one that – with its online catalogue of peptides, peptide synthesis reagents and combinatorial chemistry products, together with its peptide library design tools – could easily be mistaken for a consumer website. However, and especially given the current attention related to the AFL scandal and the alleged use of AOD-9604, an anti-obesity peptide which is prohibited from use by sportsmen by the World Anti-Doping Agency, it is important to stress that Mimotopes has never and will never knowingly supply such products or allow its peptides to be used for such purposes.

Surprising as it may seem, there is little or no national or international regulation of the supply of these little bundles of amino acids and Sonja says there is nothing that requires her company or anyone else to background-check the customer or their reasons for buying peptides. They are seen as being research tools or items, not for human use per se, and therefore attract no official supervision. “All of our customers have to demonstrate that they are associated with an R&D laboratory or bona fide university or similar establishment. We are not required to do this [check], but we do,” she explains.

In fact the AFL scandal, and the investigations by Australia’s own anti-doping agency, are starting to highlight this deficiency. There are a lot of peptide suppliers from whom you can buy on the internet; Sonja says she believes many of these substances are not fit (or indeed appropriate) for human use, “but people are actually buying them although they don’t know any better.” Such customers inevitably include the bodybuilding fraternity. Mimotopes receives a number of enquiries every week from people who “you can tell, immediately, they want to use the peptides for self-injection.”

It need hardly be added that every such enquiry is rejected – but perhaps a long-term beneficial outcome of the WADA-ASADA enquiry might be some controls both in Australia and beyond that might protect such people from incidental self-harm and help clean up sport (possibly along lines parallel to the TGA which monitors foodstuffs). Peptides and related chemistry are of enormous benefit to medical science but, like most things, can be misused. As the innovator and leader in the field, Sonja and Mimotopes are firmly of the belief that misuse should be more closely monitored for the health of the whole of the reputable industry. “Something should be done to ensure people cannot just buy peptides from the web,” she says – especially sites that include a bottle of saline to go with the peptide, something that would only be used to clean an injecting needle.

From its inception, Mimotopes’ market was largely global, a very large percentage of its work being for export. However, the company’s very success has changed the entire complexion of the marketplace, with so many peptide synthesisers and the development of own-brand peptide libraries in countries such as China and India (where labs tend to rely more on manual work and less on computer analysis and automation). So Sonja says the market is a lot more cost-conscious and her company’s emphasis is more and more on the high end. “We have changed our product mix and tried to focus more on high-value peptides,” she explains. “We work very closely with our customers to carry out innovative chemistry or modify peptides with their input. A lot of our business today is highly specialised customised work.”

At present there are six labs in Melbourne together with three peptide synthesisers (one of them a microwave synthesiser) and all the other facilities required for batch manufacture and libraries. The company’s staff of around 40 includes experts who work on leading-edge research. Despite the way peptides have developed and the market has become commoditised as a by-product of Mimotopes’ own success, Sonja says she is confident there is sufficient potential in the sector to keep her experts busy for the foreseeable future. “There is still a lot of scope,” she says.

Nearly everyone can make their own peptides these days; but what remains tricky is the delivery system, increasing the bio-availability of the peptides. “That is where a lot of the focus is going and where we have an advantage over a lot of the commodity suppliers.” It is no wonder Mimotopes is continuing to enjoy ongoing success in its field.

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July 19, 2018, 7:57 PM AEST