Varian extends NMR use into biological solids
for the first time can be used to determine the molecular
structures of proteins and other biomolecules in the solid state.
Developed in collaboration with scientists at the University of Illinois at Urbana-Champaign (UIUC), the new Bio-MAS Probe incorporates a patent-pending scroll coil design to reduce unwanted heating by three orders of magnitude compared to a standard probe. This heating effect has been one of the main impediments to the use of NMR for biological molecules, as it can destroy the samples. The new probe also has been shown to extend a sample's viable experimental lifetime by more than an order of magnitude, according to Varian.
For bio-solids NMR studies, many samples are analysed in the presence of salts; however the presence of these salts leads to undesirable heating that can denature the sample proteins, compromising experiment results and efficacy.
"The samples used for bio-solids experiments are expensive and difficult to come by, and their loss by thermal denaturation can represent a major threat to research programs," said Jan Tschida, vice president and general manager of NMR and magnetic resonance imaging (MRI) systems at Varian.
Important, the ability to carry out bio-solids NMR experiments will allow access to the 70 per cent of all cellular proteins, such as membrane proteins, that are considered solids because they are not free floating in intracellular fluid. Such studies could provide researchers with unparalleled insight into proteins and biomarker molecules associated with a wide variety of diseases.
Unlike the solenoid coils used in all current solid state NMR probes, Varian's new Bio-MAS probe's unique scroll coil design is more tolerant of high sample salt concentrations and causes less sample heating, which prolongs the sample's integrity. The new coil design also improves radiofrequency homogeneity, which helps boost sensitivity for complex bio-solids experiments.
"The combination of homogeneity, improved sensitivity, and tolerance for high dielectric [non-conducting] samples will be especially beneficial for application of solid state NMR experiments to study large membrane proteins," said Dr Chad Rienstra, assistant professor of Chemistry at UIUC.
"With solenoid-based designs, many researchers have been unable to apply the most sophisticated pulse sequences to their most important samples, due to their fear of sample damage," he continued.
Now that this concern has been eliminated, researchers will have a new tool for solving protein structures. "We believe that the impact on structural biology will be extremely important," said Rienstra.
NMR is the preferred non-destructive technique for mapping molecular structures and learning how molecules function and relate to each other, including protein structure, function and dynamics. It is also used as a workhorse technology by pharmaceutical and life science researchers for mixture analysis and small molecule structure elucidation.
An NMR probe holds the molecular sample within the bore of the magnet, at the centre of the magnetic field, and it transmits and detects radiofrequency signals that are then analysed with software to produce structural information.
Varian is currently taking orders for its new Bio-MAS probe line, featuring probes for bio-solids NMR systems operating at fields of 500 MHz and higher.
