This proposal outlines investigation of proteins and model systems with three innovative magnetic resonance techniques: high frequency dynamic nuclear polarization (DNP), time domain 140 GHz electron paramagnetic resonance (EPR), and electron nuclear double resonance (ENDOR). The research plan is divided into four Specific Aims: (1) Development of CW and Pulsed DNP methods involving high Ble fields, the CROSS-effect, and electron-nuclear cross polarization. (2) Applications of DNP to biological problems include studies of alpha-spectrin SH3 crystals, oriented bacteriorhodopsin and Pfl bacteriophage, amyloid fibrils, and O-17 MQMAS. Each of these projects involves an area of magnetic resonance where the enhanced signal intensities available with DNP could have a significant impact. (3) Investigations of pulsed EPR and ENDOR investigations for four different systems: (a) the """"""""3- minute"""""""" radical observed in the E441Q mutant of ribonucleotide reductase (RNR); (b) a model for the X-intermediate formed on combining Fe and apoRNR, and the X-intermediate in the protein itself; (c) the tyrosyl radical in RNR from yeast; (d) study of a difluorinated inhibitor of RNR, gemcitabine, with both Class I and Class II RNR's. (4) Development of advanced pulsed EPR/ENDOR at 140 GHz. These include TRIPLE, TRAPS, DEER and MQENDOR with the goal of enhancing the versatility and resolution of methods available to examine protein free radicals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
8R01EB002804-15
Application #
6625062
Study Section
Special Emphasis Panel (ZRG1-BMT (01))
Program Officer
Mclaughlin, Alan Charles
Project Start
1987-04-01
Project End
2004-11-30
Budget Start
2002-12-03
Budget End
2003-11-30
Support Year
15
Fiscal Year
2003
Total Cost
$481,856
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
Wittmann, J J; Can, T V; Eckardt, M et al. (2018) High-precision measurement of the electron spin g factor of trapped atomic nitrogen in the endohedral fullerene N@C60. J Magn Reson 290:12-17
Ji, X; Can, T V; Mentink-Vigier, F et al. (2018) Overhauser effects in non-conducting solids at 1.2?K. J Magn Reson 286:138-142
Frederick, Kendra K; Michaelis, Vladimir K; Caporini, Marc A et al. (2017) Combining DNP NMR with segmental and specific labeling to study a yeast prion protein strain that is not parallel in-register. Proc Natl Acad Sci U S A 114:3642-3647
Can, Thach V; Weber, Ralph T; Walish, Joseph J et al. (2017) Frequency-Swept Integrated Solid Effect. Angew Chem Int Ed Engl 56:6744-6748
Jain, Sheetal K; Mathies, Guinevere; Griffin, Robert G (2017) Off-resonance NOVEL. J Chem Phys 147:164201
Ni, Qing Zhe; Yang, Fengyuan; Can, Thach V et al. (2017) In Situ Characterization of Pharmaceutical Formulations by Dynamic Nuclear Polarization Enhanced MAS NMR. J Phys Chem B 121:8132-8141
Ni, Qing Zhe; Markhasin, Evgeny; Can, Thach V et al. (2017) Peptide and Protein Dynamics and Low-Temperature/DNP Magic Angle Spinning NMR. J Phys Chem B 121:4997-5006
Colvin, Michael T; Silvers, Robert; Ni, Qing Zhe et al. (2016) Atomic Resolution Structure of Monomorphic A?42 Amyloid Fibrils. J Am Chem Soc 138:9663-74
Kaushik, Monu; Bahrenberg, Thorsten; Can, Thach V et al. (2016) Gd(iii) and Mn(ii) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins. Phys Chem Chem Phys 18:27205-27218
Mathies, Guinevere; Jain, Sheetal; Reese, Marcel et al. (2016) Pulsed Dynamic Nuclear Polarization with Trityl Radicals. J Phys Chem Lett 7:111-6

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