When working to create a new therapy, drug or compound, scientists must learn more about the properties of the molecules involved and how they interact with each other. Similar to how an MRI scanner can show anatomical structure and physiological processes inside the body, high-resolution nuclear magnetic resonance (NMR) spectroscopy can characterize the structure, dynamics, reaction state and chemical environment of biomolecules, small organic compounds and natural products through the observation of local magnetic field perturbations around atomic nuclei.
At City of Hope, the Nuclear Magnetic Resonance (NMR) Core facility, led by Yuan Chen
, Ph.D., dean of transdisciplinary research and professor in the Department of Molecular Medicine
, and Weidong Hu
, Ph.D., research professor in the Department of Molecular Imaging & Therapy
, has helped facilitate research on campus in structure identification for ligands, which are small molecules that transmit signals in between or within cells, as well as ligand quality checking, and ligand and protein interaction.
The NMR Core is also equipped to assist in explorations of protein-protein interactions and protein and nucleic acid interactions, and in metabolomics studies of cell-based and mouse tissue. Metabolomics data can give information on the metabolites involved in specific cellular processes in order to compare cells under different conditions, such as healthy versus diseased or drug-treated versus non-treated.
“We have been a key part of a wide range of studies that have generated a lot of publications,” said Hu. “For example, the NMR Core helped in the early stages of the discovery of a potential anti-cancer drug, COH29, that is in the clinical trial stage now.” COH29 is a chemotherapy drug that specifically targets an enzyme called ribonucleotide reductase, preventing cancer cells from copying themselves and dividing and hopefully causing fewer side effects than other regimens.
The NMR Core at City of Hope consists of one 600 MHz Bruker Avance instrument and one 700 MHz Bruker Ascend instrument. While the 700 MHz instrument offers better NMR signal sensitivity and resolution, both instruments are equipped with cryoprobes that help deliver a much higher signal sensitivity than traditional room-temperature probes. The NMR Core facility also offers access to the commercial software, Chenomx, used for metabolomics studies, as well as to free software for similar studies and also for biomolecular characterization. Use of the instruments is mainly focused on, but not limited to, biomolecular characterization, and Chen said they are well-suited to carry out a variety of different NMR applications.
“The instruments in the NMR Core provide a shared resource that is not available through other contract research organizations or nearby academic institutions,” she added.
Currently the NMR Core is not directly involved in patient studies, but the instruments have been used to look at patient cells, such as hematopoietic stem cells from patients in biomarker analysis. In addition, there are potential promising applications of the NMR spectroscopy in metabolomics, Hu said.
“For use in a hospital environment, the potential applications include disease diagnosis, biomarker identification, drug testing and treatment followups,” he said. “It could be a very useful and noninvasive tool for diagnoses and for monitoring the treatment of tumors and even diabetes.”