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A New (Bio)Spin on NMR Applications

By Robert M. Frederickson

May 12, 2006 | Nuclear magnetic resonance (NMR) plays an increasing role in structural genomic efforts that aim to complement primary sequence analyses of proteins on a genomewide scale. Between 15 percent and 20 percent of the protein structures deposited in the Protein Data Bank have their origin in macromolecular structures solved by NMR methods. Today, sophisticated NMR experiments together with computational methods significantly reduce the time needed for NMR structure determination, and providers of NMR analysis hardware and software have responded accordingly to facilitate application of automated NMR in drug discovery.

When we think of protein structure determination, we usually think of X-ray crystallography and mass spectroscopy. While mass spectroscopy may provide advantages with regards to sensitivity, NMR is a powerful tool to study the structures, dynamics, and interactions of biological molecules in solution. This ability facilitates a more physiological analysis than the use of crystallized molecules, whose structure is nondynamic and often not fully representative of the physiological folding of a protein, for example. NMR can also provide structural information where a crystal is unavailable.

The applications of NMR in drug discovery go beyond protein structure determination, however. NMR can be used to screen for small molecules or other proteins that interact with a protein drug target of choice. NMR has been shown to be more sensitive to weak interactions than other methods, facilitating the screening of libraries for interacting molecules. NMR also has applications in metabolic profiling and toxicology, and in imaging molecules of interest in cells, tissues, and even whole animals.

Bruker BioSpin recently announced several introductions to improve throughput, sensitivity, and versatility of its systems for NMR applications starting with the SampleJet, a robotics system for high-throughput transfers of NMR sample tubes into the NMR spectrometer. The SampleJet complements Bruker BioSpin’s NMR sample handling systems, including tube-based and flow-injection automation. SampleJet was designed and developed in collaboration with the pharmaceutical and chemical industries to address the need for fast turnover of large amounts of NMR samples together with routine walk-up capabilities. The SampleJet installs on top of virtually any Bruker BioSpin NMR magnet with no need for additional laboratory space and is controlled by Bruker BioSpin’s automation software, IconNMR.

Magnetic Personality
NMR analysis requires a strong magnetic field produced by immense magnets. The magnetic field produced by the magnet gives rise to resonance of the nuclei of particular atoms — such as hydrogen, carbon, or nitrogen — that can provide information as to their identity and location within a larger molecule. The NMR spectra produced by particular molecules — even large molecules such as proteins — are specific and can be used for both qualitative and quantitative analyses and information on the dynamic interaction of ligands and proteins.

Sensitivity is an important consideration for NMR analyses, and cryogenically cooled probes can improve the signal-to-noise ratio by three to four fold. As a result, they are capable of measuring lower concentrations and enable experiments to be completed as much as 16 times more quickly. Bruker BioSpin recently introduced the QNP CryoProbe for multipurpose NMR measurements of four different nuclei — phosphorus, carbon, nitrogen, and hydrogen. This 5-mm, general-purpose, cryogenically cooled probe is automated to easily switch between these nuclei, eliminating the need to change probes. The four nuclei are present individually or together in a majority of organic, biological, and inorganic compounds. Direct observation of these nuclei can provide quantitative information in addition to small-molecule structural data. The most significant advantage of this new probe is that it enables more complete characterization of molecules that contain all four of these nuclei.

Bruker BioSpin has also unveiled the 800 MHz UltraShield Plus actively shielded NMR magnet, with a significant reduction in size and magnetic stray field compared to other 800-MHz magnets.

E-mail Robert M. Frederickson at

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