Despite its importance as a versatile tool in many chemical analyses, nuclear magnetic resonance (NMR) spectroscopy suffers from its poor sensitivity and sample throughput capabilities. This proposal describes a program to make a significant improvement in the throughput of NMR measurements. A new approach, Multiplex NMR, can simultaneously measure the NMR signals from multiple samples. The proposal focuses on five areas of fundamental research to develop this new technology to the point where it can be useful for a wide range of NMR measurements of interest to the biomedical community.
Specific Aims : 1. Develop and test methods for high speed data acquisition on combinatorial peptide libraries 2. Develop 2D NMR methods for simultaneous analysis of multiple samples and faster LC/NMR 3. Increase sensitivity and parallelism to 8 or more samples using micro-fabrication methods 4. Improve sensitivity using inline sample pre-concentration methods 5. Explore the use of parallel NMR coils for solvent suppression and NMR difference spectroscopy. The long-term goal of this research is to provide order of magnitude improvements in the throughput of single- and multi-dimensional NMR measurements. Applications in areas such as combinatorial chemistry, high throughput screening, organic synthesis and biological chemistry will benefit from the development of the approach described in this proposal. Two specific biomedical applications of the new technology involving the analysis of combinatorial peptide libraries and the study of protein-ligand interactions are described.
| Mo, Huaping; Harwood, John; Zhang, Shucha et al. (2009) R: A quantitative measure of NMR signal receiving efficiency. J Magn Reson 200:239-44 |
| Bergeron, Scott J; Henry, Ian D; Santini, Robert E et al. (2008) Saturation transfer double-difference NMR spectroscopy using a dual solenoid microcoil difference probe. Magn Reson Chem 46:925-9 |
| Djukovic, Danijel; Appiah-Amponsah, Emmanuel; Shanaiah, Narasimhamurthy et al. (2008) Ibuprofen metabolite profiling using a combination of SPE/column-trapping and HPLC-micro-coil NMR. J Pharm Biomed Anal 47:328-34 |
