9 June 2011
A small team of researchers from the Monash Institute of Pharmaceutical Sciences (MIPS) has taken significant steps toward a more efficient method in drug design. They have developed a new tool that has the potential to influence the way pharmaceutical drugs are designed, fast tracking their creation and resulting in more effective drugs.
For over two years, Dr James Swarbrick and Dr Bim Graham from the Department of Medicinal Chemistry, along with PhD students Phuc Ung and Sandeep Chharbra, have been working together on the development of new technologies to assist with drug discovery.
Their new tool consists of a small synthetic tag that can be used to connect single metal atoms to the surface of a protein. This changes the properties of the atoms in the protein, leading to a range of interesting effects that can be observed by Nuclear Magnetic Resonance (NMR) spectroscopy – a technique used widely in chemical and biochemical research to determine the structure of molecules.
According to Dr Swarbrick, analysis of the effects produced by attaching metal atoms to disease-related proteins is very useful in helping to work out their three-dimensional structure, as well as in designing new drugs to target them.
“This new tag has great potential in the determination of protein structures from a minimal number of NMR experiments, resulting in less time spent in the laboratory,” Dr Swarbrick said.
Dr Bim Graham explained that the novelty of the group’s work stems from the unique tag design.
"We sought to come up with the smallest, simplest structure that could be used to connect a metal ion to the surface of a protein in a reliable and predictable way. The new tag allows us to collect extremely useful information that can’t be obtained with existing tools,” Dr Graham said.
This is the first time the researchers have collaborated together on a major project, drawing on Dr Graham’s knowledge of creating synthetic molecular structures and Dr Swarbrick’s expertise in biomolecular NMR spectroscopy and structural biology.
"We saw a unique opportunity to make a valuable contribution by combining our expertise from different fields. Researchers realise the importance of collaboration, and working in an environment like the Monash Institute of Pharmaceutical Sciences (MIPS) enables us to establish these links easily," Dr Swarbrick said.
The research team is now hoping to employ the new tag and methodology in a range of drug screening and structural biology projects at MIPS.
"The results of our work are not immediately apparent to consumers with the medicines they take, but for the researchers working behind the scenes to develop these drugs, the new tool represents a significant step forward that will ultimately result in the faster production of more effective drugs for treating people's conditions," Dr Graham said.
The work has been published in the May edition of the prestigious journal Angewandte Chemie.
An Iminodiacetic Acid Based Lanthanide Binding Tag for Paramagnetic Exchange NMR spectrsocopy
James D Swarbrick, Phuc Ung, Sandeep Chhabra and Bim Graham.
Angew Chem Int Ed (2011), 50, 4403-4406.