Duncan NRI NMR and Drug Metabolism Core

The NMR and Drug Metabolism Core, part of the Intellectual and Developmental Disability Research Center (IDDRC) and situated on the 2^nd and 6^th floors of the Duncan NRI building, offers expertise in NMR and Liquid Chromatography-Mass Spectrometry (LC-MS) in support of synthetic chemistry, structural biology, fragment-based ligand discovery, metabolomics, biomarker discovery, and drug metabolism. It offers state-of-the-art tools required for the discovery, synthesis, screening, optimization, metabolism, metabolic stability and pharmacokinetics of small molecule ligands or lead compounds. 

The core hosts two Bruker Avance III HD NMR spectrometers (600 MHz and 800 MHz) with a quadruple resonance cryoprobe at 800 MHz as well as a Thermo Scientific™ Q Exactive™ mass spectrometer with high-resolution, accurate-mass Orbitrap™ detection (used for drug metabolism/pharmacokinetics and untargeted metabolomics) and a 6490 Triple Quadrupole mass spectrometer (QQQ, Agilent Technologies, Santa Clara, CA) with a UHPLC front end, used to assay xenobiotics in animal and human biofluids and tissue samples. Expert services are available to determine small molecule identity or conformation, to identify and quantify metabolites, to determine macromolecular structure or detect perturbations upon ligand binding, or to screen compound libraries against purified targets.

By late 2023, this Core will also offer mass spectrometry imaging platform, a powerful molecular imaging technology bringing unparalleled molecular specificity and sensitivity to map the distribution of small molecules and metabolites in tissues. This technology uses existing mass spectrometry detection platforms to visualize, map, and analyze with unprecedented resolution hundreds of these molecules at the same time, in a single, label-free tissue section without any need for specific molecular probes.

Core personnel provide advice on the use of the supported methods for a wide variety of applications and assistance is available in project experimental design and data analysis.

Core Services

• The high-field NMR instrumentation is available to all Texas Medical Center researchers for spectroscopy applications that range from simple 1D acquisitions lasting several minutes, to multi-dimensional/multi-nuclear investigations of macromolecule structure and dynamics lasting many hours, to ligand/macromolecule binding screens that analyze hundreds of samples and thousands of compounds over the course of days.
• The 600 and 800 MHz Bruker NMR spectrometers are available for unassisted use by trained individuals at all hours, subject to availability on a public calendar. User training in simple 1D and 2D NMR data acquisition and analysis can be provided.
• NMR data acquisition and analysis are also available through the core on a fee-for-service basis. The versatility of our instrumentation means we can tackle many kinds of experiments; common examples are listed below, but please inquire about other NMR approaches not listed.
• NMR requests for service should briefly indicate the type of sample and the question being addressed, and core personnel will be in touch to discuss possible ways to proceed. No charges are incurred for initial consultations or discussion of experimental design. We encourage the use of fee-for-service NMR as an initial foray, e.g. to obtain preliminary data for a grant, which then allows the researcher to decide whether or not to commit more resources based on the outcome of the experiments and of the availability of funding.
• Core personnel can help with grant-writing efforts that incorporate proposed NMR experiments and/or NMR preliminary data. Letters of support and personnel bio-sketches tailored to the needs of the proposal and indicating the availability of the core and its expertise are available upon request.