New magnetic spectrometer will assist in drug research

David Hyland

University officials lured a prominent scientist away from Yale two years ago with the promise of a $3 million tool that will help him and others study the building blocks of life.
As early as this month, Ian Armitage might get his new spectrometer, the most powerful and only one of its kind in the world.
The machine is expected to boost efforts to provide new and enhanced drug treatments through nuclear magnetic resonance research. It involves using high-field magnets to observe the building blocks of molecules in biology, everything from DNA to carbohydrates to proteins.
“What we have here is a nuclear magnetic resonance lab that is pretty close to second to none in North America,” said Armitage, director of the University’s nuclear magnetic resonance program.
Nuclear magnetic resonance provides images that allow researchers to deduce the structure of bio-molecules and the dynamics and motion of those molecules.
However, the “nuclear” in nuclear magnetic resonance is not in the sense of nuclear power or weapons. Rather, it refers to the nuclei of such molecules of carbohydrates and proteins.
On the most basic level, spectrometers allow researchers to reconstruct images of various biological molecules.
The spectrometer creates a high magnetic field, almost 200,000 times stronger than the earth’s magnetic field. The field causes the nuclei to align their “magnetic moments,” similar to how the north pointer on a compass aligns with the Earth’s magnetic field and points north.
The second phase of the process involves a radio transmitter that sends signals that offset the nuclei’s equilibrium. The nuclei then emit radio frequencies and return to a normal state of balance. These signals are received by the spectrometer’s receiver.
“The real payoff is what the structure is and what it informs you about the biological system,” said David Live, the lab’s facility manager.
Kevin Mayo, a professor of biochemistry, said the information gathered from nuclear magnetic resonance has given scientists greater insight into the structures and activity of the atoms. It aids them in creating better drugs that are more effective and cause fewer side effects.
Mayo has used the information from two lower-powered spectrometers at the University to study the structures of proteins and peptides to come up with new drugs that impede tumor growth.
Resembling giant milk vats, the stainless steel cylindrical spectrometers are kept cold with liquid nitrogen and liquid helium to maintain the superconductivity of the magnets.
The lab that houses the devices is used by almost a dozen researchers in the biochemistry, chemistry, chemical engineering, radiology, medicinal chemistry and pharmacy departments.
The new Basic Sciences and Biomedical Engineering building was specifically designed to house the program’s $2 million, state-of-the-art lab. Located in the basement, the lab offers not only space for the three magnets but isolation from vibrations from the building (like those from elevators), which lessen the sensitivity of the equipment.
Expected to arrive soon, the new 800 MHz spectrometer will be on “the cutting edge,” Armitage said. He said the higher magnetic field provides greater sensitivity. It far outpaces smaller spectrometers researchers are currently using, he said.
“The magnets that we have down there now, the 500 MHz and 600 MHz, are no longer unique. They were only unique 15 years ago,” Armitage said. “The 800 MHz is something that not every location is going to have.”
Because nuclear magnetic resonance spectroscopy is such a highly specialized technique with no “superficially obvious” results, Live said the public and scientists have largely ignored its importance.
Armitage suspects private companies and other universities will want to buy time to use the new spectrometer for some of their projects.
Both Armitage and Live said increased sensitivity with an enhanced spectrometer will be more valuable in years to come.
“I want and strive to see it used more extensively in the research programs of faculty,” Armitage said. “We really do have the opportunity to break new ground in science and NMR. There are observations and phenomena that will open new doors to research.”