Nuclear Magnetic Resonance Facility

Nuclear magnetic resonance (NMR) spectroscopy is a solution-based technique used to probe the structure and dynamics of molecules, ranging from small molecules to proteins. The NMR facility at MUSC comprises three NMR spectrometers with field strengths of 400 and 600. The 400 MHz spectrometer is used mainly for small molecule analysis and has two broadband probes. The 600 MHz spectrometer is primarily used for biomolecular research, including solving high-resolution structures of macromolecules, measuring drug/protein interactions and metabolomics. The facility is housed within a custom-built laboratory on the first floor of the Drug Discovery Building.

The NMR facility can be accessed in two ways:

1. Trained users can access the spectrometers on an hourly-fee basis.
2. For those without NMR expertise, experiments can be performed by the Facility Manager, in which case additional fees will apply to cover time spent.

For extended projects, a percentage effort coverage of the Facility Manager can be negotiated.

Recent Publications

Carruthers, N. J., Stemmer, P. M., Media, J., Swartz, K., Wang, X., Aube, N., Hamann, M. T., Valeriote, F., & Shaw, J. (2020). The anti-MRSA compound 3-O-alpha-L-(2″,3″-di-p-coumaroyl)rhamnoside (KCR) inhibits protein synthesis in Staphylococcus aureus. Journal of Proteomics, 210, 103539. https://doi.org/10.1016/j.jprot.2019.103539

Chen, X., Ding, Y., Forrest, B., Oh, J., Boussert, S. M., & Hamann, M. T. (2019). Lemon yellow #15 a new highly stable, water soluble food colorant from the peel of Citrus limon. Food Chemistry, 270, 251–256. https://doi.org/10.1016/j.foodchem.2018.07.055

Liu, J., Pandey, P., Wang, X., Adams, K., Qi, X., Chen, J., Sun, H., Hou, Q., Ferreira, D., Doerksen, R. J., Hamann, M. T., & Li, S. (2019). Hepatoprotective Tetrahydrobenzocyclooctabenzofuranone Lignans from Kadsura longipedunculata. Journal of Natural Products, 82(10), 2842–2851. https://doi.org/10.1021/acs.jnatprod.9b00576

Wang, X., & Hamann, M. T. (2019). Marine natural products in the discovery and development of potential pancreatic cancer therapeutics. Advances in Cancer Research, 144, 299–314. https://doi.org/10.1016/bs.acr.2019.05.003

Zou, Y., Wang, X., Sims, J., Wang, B., Pandey, P., Welsh, C. L., Stone, R. P., Avery, M. A., Doerksen, R. J., Ferreira, D., Anklin, C., Valeriote, F. A., Kelly, M., & Hamann, M. T. (2019). Computationally Assisted Discovery and Assignment of a Highly Strained and PANC-1 Selective Alkaloid from Alaska's Deep Ocean. Journal of the American Chemical Society, 141(10), 4338–4344. https://doi.org/10.1021/jacs.8b11403

Holshouser, S., Dunworth, M., Murray-Stewart, T., Peterson, Y. K., Burger, P., Kirkpatrick, J., Chen, H. H., Casero, R. A., Jr, & Woster, P. M. (2019). Dual inhibitors of LSD1 and spermine oxidase. MedChemComm, 10(5), 778–790. https://doi.org/10.1039/c8md00610e

El Bissati, K., Redel, H., Ting, L. M., Lykins, J. D., McPhillie, M. J., Upadhya, R., Woster, P. M., Yarlett, N., Kim, K., & Weiss, L. M. (2019). Novel Synthetic Polyamines Have Potent Antimalarial Activities in vitro and in vivo by Decreasing Intracellular Spermidine and Spermine Concentrations. Frontiers in Cellular and Infection Microbiology, 9, 9. https://doi.org/10.3389/fcimb.2019.0000

Holshouser, S., Dunworth, M., Murray-Stewart, T., Peterson, Y. K., Burger, P., Kirkpatrick, J., Chen, H. H., Casero, R. A., Jr, & Woster, P. M. (2019). Dual inhibitors of LSD1 and spermine oxidase. MedChemComm, 10(5), 778–790. https://doi.org/10.1039/c8md00610e

Kumarasinghe, I.; Casero, Jr., R.A.; Woster, P.M.: D-Amino acid-substituted cyclic peptides with enhanced activity against lysine-specific demethylase 1. Bioorg. Med. Chem. 2019, submitted.

De Palma, R. M., Parnham, S. R., Li, Y., Oaks, J. J., Peterson, Y. K., Szulc, Z. M., Roth, B. M., Xing, Y., & Ogretmen, B. (2019). The NMR-based characterization of the FTY720-SET complex reveals an alternative mechanism for the attenuation of the inhibitory SET-PP2A interaction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(6), 7647–7666. https://doi.org/10.1096/fj.201802264R

Zou, Y., Wang, X., Sims, J., Wang, B., Pandey, P., Welsh, C. L., Stone, R. P., Avery, M. A., Doerksen, R. J., Ferreira, D., Anklin, C., Valeriote, F. A., Kelly, M., & Hamann, M. T. (2019). Computationally Assisted Discovery and Assignment of a Highly Strained and PANC-1 Selective Alkaloid from Alaska's Deep Ocean. Journal of the American Chemical Society, 141(10), 4338–4344. https://doi.org/10.1021/jacs.8b11403

Young, B. F., Roth, B. M., & Davies, C. (2019). 1H, 13C, and 15N resonance assignments of N-acetylmuramyl-L-alanine amidase (AmiC) N-terminal domain (NTD) from Neisseria gonorrhoeae. Biomolecular NMR Assignments, 13(1), 63–66. https://doi.org/10.1007/s12104-018-9852-1

Kumarasinghe, I. R., & Woster, P. M. (2018). Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency identified by alanine scanning mutagenesis. European Journal of Medicinal Chemistry, 148, 210–220. https://doi.org/10.1016/j.ejmech.2018.01.098

Kirkpatrick, J. E., Kirkwood, K. L., & Woster, P. M. (2018). Inhibition of the histone demethylase KDM4B leads to activation of KDM1A, attenuates bacterial-induced pro-inflammatory cytokine release, and reduces osteoclastogenesis. Epigenetics, 13(5), 557–572. https://doi.org/10.1080/15592294.2018.1481703

Wang, X., Liu, J., Pandey, P., Fronczek, F. R., Doerksen, R. J., Chen, J., Qi, X., Zhang, P., Ferreira, D., Valeriote, F. A., Sun, H., Li, S., & Hamann, M. T. (2018). Computationally Assisted Assignment of the Kadsuraols, a Class of Chemopreventive Agents for the Control of Liver Cancer. Organic Letters, 20(18), 5559–5563. https://doi.org/10.1021/acs.orglett.8b02207

Park, H. B., Tuan, N. Q., Oh, J., Son, Y., Hamann, M. T., Stone, R., Kelly, M., Oh, S., & Na, M. (2018). Sesterterpenoid and Steroid Metabolites from a Deep-Water Alaska Sponge Inhibit Wnt/β-Catenin Signaling in Colon Cancer Cells. Marine Drugs, 16(9), 297. https://doi.org/10.3390/md16090297

Simithy, J., Fuanta, N. R., Alturki, M., Hobrath, J. V., Wahba, A. E., Pina, I., Rath, J., Hamann, M. T., DeRuiter, J., Goodwin, D. C., & Calderón, A. I. (2018). Slow-Binding Inhibition of Mycobacterium tuberculosis Shikimate Kinase by Manzamine Alkaloids. Biochemistry, 57(32), 4923–4933. https://doi.org/10.1021/acs.biochem.8b00231

Liu, D. S., Rong, X. G., Kang, H. H., Ma, L. Y., Hamann, M. T., & Liu, W. Z. (2018). Raistrickiones A-E from a Highly Productive Strain of Penicillium raistrickii Generated through Thermo Change. Marine Drugs, 16(6), 213. https://doi.org/10.3390/md16060213

Chen, X. Y., Zhang, T., Wang, X., Hamann, M. T., Kang, J., Yu, D. Q., & Chen, R. Y. (2018). A Chemical Investigation of the Leaves of Morus alba L. Molecules (Basel, Switzerland), 23(5), 1018. https://doi.org/10.3390/molecules23051018

Simithy, J., Fuanta, N. R., Hobrath, J. V., Kochanowska-Karamyan, A., Hamann, M. T., Goodwin, D. C., & Calderón, A. I. (2018). Mechanism of irreversible inhibition of Mycobacterium tuberculosis shikimate kinase by ilimaquinone. Biochimica et Biophysica Acta. Proteins and Proteomics, 1866(5-6), 731–739. https://doi.org/10.1016/j.bbapap.2018.04.007

Liu, J., Pandey, P., Wang, X., Qi, X., Chen, J., Sun, H., Zhang, P., Ding, Y., Ferreira, D., Doerksen, R. J., Hamann, M. T., & Li, S. (2018). Hepatoprotective Dibenzocyclooctadiene and Tetrahydrobenzocyclooctabenzofuranone Lignans from Kadsura longipedunculata. Journal of Natural Products, 81(4), 846–857. https://doi.org/10.1021/acs.jnatprod.7b00934

Wang, X., Liu, J., Pandey, P., Chen, J., Fronczek, F. R., Parnham, S., Qi, X., Doerksen, R. J., Ferreira, D., Sun, H., Li, S., & Hamann, M. T. (2017). Assignment of the absolute configuration of hepatoprotective highly oxygenated triterpenoids using X-ray, ECD, NMR J-based configurational analysis and HSQC overlay experiments. Biochimica et Biophysica Acta. General Subjects, 1861(12), 3089–3095. https://doi.org/10.1016/j.bbagen.2017.09.001

Ibrahim, M. A., El-Alfy, A. T., Ezel, K., Radwan, M. O., Shilabin, A. G., Kochanowska-Karamyan, A. J., Abd-Alla, H. I., Otsuka, M., & Hamann, M. T. (2017). Marine Inspired 2-(5-Halo-1H-indol-3-yl)-N,N-dimethylethanamines as Modulators of Serotonin Receptors: An Example Illustrating the Power of Bromine as Part of the Uniquely Marine Chemical Space. Marine Drugs, 15(8), 248. https://doi.org/10.3390/md15080248

Nuclear Magnetic Resonance Core Administration

The facility is directed by Yuri K. Peterson, Ph.D., Associate Professor of Drug Discovery and Biomedical Sciences. An Advisory Board provides guidance for the operations of the NMR facility and its instruments including:

• Recommending policies and procedures for allocation of spectrometer time, usage fees, maintenance, and future grant proposals submitted on behalf of the facility.
• Providing guidance for ensuring a safe, environmentally friendly, and secure work environment, including emergency and disaster planning.
• Reviewing the financials of the facility
• Monitoring the output of the facility in terms of publications and grant awards

The current members of the NMR Advisory Board are:

• Mark Hamann, Ph.D., College of Pharmacy
• Besim Ogretmen, Ph.D., College of Medicine
• Yuri K. Peterson, Ph.D., College of Pharmacy

Nuclear Magnetic Resonance Instruments

The NMR facility maintains two spectrometers used for a variety of applications, including structure determination of small molecules or proteins, metabolomics, and binding studies using saturation transfer dispersion (STD).

MUSC 600MHz Spectrometer

A shielded 600MHz Bruker Avance II spectrometer incorporates the latest digital receiver technology for a significant improvement in NMR sensitivity and facilitates operations in a four-channel setup. Available Probes: 5mm triple resonance (TXI; H- C-N): single-axis gradient, ATM 5mm quadruple resonance (QXI; H-F-C, P) triple-axis gradients. Additionally a recent equipment grant award has allowed us to purchase a QCI-cryoprobe to further enhance the sensitivity of our system by 400%. The QCI probe is a proton-optimized quadruple resonance NMR inverse probe (QCI; H-F, C, N, P) a modification to the proton coil will allow us to tune to 19F thereby increasing application use with minimal sacrifice to sensitivity. The probe allows for decoupling on multiple nuclei such as 13C, 31P and 15N; and is equipped with cold preamplifiers for 1H, 13C and 31P.

MUSC 400MHz Spectrometer

A Bruker Nanobay- 400 (9.4 T), operating at 400MHz proton, provides a moderately high field multi-nuclear NMR capability to MUSC and the College of Charleston. The Bruker Nanobay- 400, a top-of-the-line spectrometer, is capable of running most contemporary homonuclear, heteronuclear one and two-dimensional pulse sequences, using pre- designed software. The spectrometer is equipped with a 5mm Multinuclear Broadband Fluorine Observe Plus (BBFOPLUS) probe, which allows for the routine acquisition of 1D and 2D 1H-1H correlations as well as 1D 31P and 2D 1H-31P correlations. Indirectly detected 1H-13C, 1H-15N and 1H-31P spectral correlations are also routinely obtained. Directly detected 13C spectra as well as other nuclei with resonances between 39-161 MHz are also accessible. Gradient versions of some 2-dimensional pulse sequences are present as is a deuterium gradient shimming module that provides automated shimming of off-axis shims using Real-Time control board capabilities. The availability of shaped pulses allow for very selective excitation of a selected resonance, which results in much improved water suppression in peptide NMR. Because of the magnetic field strength of the spectrometer, the practical peptide molecular weight limit for meaningful interpretation of 2D spectra is 3-4kDa.

Nuclear Magnetic Resonance Publication Acknowledgement

The NMR facility is a University Research Resource Facility (URRF) and currently receives support from the Office of the Vice President for Research. Any publications that arise through the use of the NMR Facility should cite the following:

NMR data was generated through use of the MUSC NMR Core Facility. The NMR Core Facility is supported by the Office of the Vice President for Research at the Medical University of South Carolina.

Nuclear Magnetic Resonance Services & Pricing

Effective September 1st, 2019, the instrument charges for MUSC users of the NMR facility are as follows.

• 850 and 600 MHz magnets, $8/hour
• 400 MHz magnet, $9.50/hour
• Internal users of the 400 mHz NMR: $9.50/hr
• Internal users of the 600 mHz NMR: $8.00/hr
• Sample preparation by the Core: $35.00
• Samples run by Core personnel will be charged at 2X the internal rate
• External users of the 400 mHz NMR: $25.00/hr
• External users of the 600 mHz: $22.00/hr
• Samples run by Core personnel will be charged at 2X the internal rate
• Sample preparation by the Core: $35.00

*For external rates, please email the Facility Director.