50 TESTING a b c
Figure 2: (a) Deuterated recombinant protein production; (b) Deuterated biopolyester production and (c) Fast protein liquid chromatography system for protein purification.
industry, and that there is great potential to innovate and market new or improved products in the manufacturing sector, including the cosmetic industry. The provision of a wide range of specialised, commercially unavailable, deuterated molecules at Australia’s only neutron facility puts NDF at a pivotal role for Australian science. The facility has a mature operational model based on biannual calls for proposals, followed by external scientific review, and attracts a wide range of users from Australia and around the world.1
National Deuteration Facility: a unique facility NDF provides two separate platforms for its molecular deuteration capabilities to external users. The first involves the biosynthesis of deuterium-labelled macromolecules and the second involves catalytic exchange of organic chemicals under high pressure and temperature in heavy water. Deuteration initiatives with a research focus are not only limited to a handful of laboratories around the world, but are also restricted in capability and diversity of applications. National and international leading
researchers are using the facility, both individually and collaboratively to investigate complex nanoscale systems in various fields (Fig 1), previously hampered
by the lack of relevant labelled molecules. Some examples are given below. This has led to publications in high impact and prestigious refereed science journals.2 Deuterium labelling of small deuterated
organic molecules, lipids, polysaccharides is a key application in developing new methodologies for studying drug metabolism by liquid chromatography and mass spectrometry. Metabolic switching, a strategy to block the site of metabolism by using deuterium to improve therapeutic profile of a drug, has been attracting a wide interest from biotechnology and drug companies. The first deuterated drug was approved by The Food and Drug Administration (FDA) in April 2017 for the treatment of chorea associated with Huntington’s disease. Quality control is essential to minimise costs in the pharmaceutical, healthcare and cosmetic industries. For instance, the distribution and size of active ingredients and/or binders and fillers (e.g. sugars, lipids) is something that requires tight control in order for constant efficacy across drug batches. The same applies to health care and beauty care blends. Imaging pharmaceutical materials using vibrational spectroscopy and deuteration is ground breaking to obtain this information and to ensure uniform solid mixing and homogeneity. This involves selective
deuterium labelling of excipients and bioactives for greater discrimination of different particles and their distributions. Combining neutron techniques and deuteration to measure directly ingredient mixing problems within operating machinery with monitoring the heterogeneity of and consistency of the product with vibrational spectroscopy in pharmaceutical industry can revolutionise the manufacture and engineering of such equipment. The NDF can provide deuterated sugars, lipids, deuterated drug precursors and final compounds, triple labelled proteins and deuterated biopolymers that are unavailable elsewhere.
Biological deuteration Biodeuteration involves the growth of microbial cultures (most commonly Escherichia coli) in heavy water (D2
O),
supplemented with either a deuterated or hydrogenated carbon compound, depending on the level of deuteration required. Five laboratories house the infrastructure for production, purification and characterisation of deuterated biomolecules (Figure 2 shows three of these laboratories).
Biodeuteration research activity Deuteration of proteins, which constitutes the majority of biodeuteration requests,
Figure 3: Three hydrothermal Parr vessels (left), Liquid Chromatography/Mass Spectrometry/Mass Spectrometry system (middle), 400 MHz NMR spectroscopy lab (right).
PERSONAL CARE ASIA PACIFIC September 2019
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