The proposed research is focused on high frequency dynamic nuclear polarization (DNP)/NMR, electron paramagnetic resonance (EPR) and electron nuclear double resonance (ENDOR). We plan CW and pulsed DNP experiments and primarily time domain EPR and ENDOR spectroscopy. The research will develop new magnetic resonance technology and methodology, and address structural questions in a number of interesting biochemical systems. DNP: The DNP experiments can be divided into four (4) areas of endeavor. (1) CW MAS-DNP focuses on the design and construction of equipment to complete a 460 GHz/700 MHz DNP/NMR spectrometer and on applications of DNP to structural biology of membrane and amyloid proteins, the soluble protein GB1 and 17O MQMAS experiments. (2) T-Jump DNP experiments for enhancing NMR signals in spectra of liquids will be developed further. (3) Biradical polarizing agents will be synthesized to improve the efficiency of DNP. (4) Pulsed DNP experiments are planned that will enhance the efficiency of electron-nuclear polarization transfer. EPR/ENDOR: We plan to address questions in five (5) areas with EPR and ENDOR. (1) We propose to develop a simple method for spin counting in proteins containing free radicals (2) We plan to develop a freeze quench apparatus and examine the kinetics of formation of short time radical intermediates in RnR chemistry. (3) We will reexamine high field EPR and ENDOR spectra of apogalactose oxidase as a path to understand the identical spectra observed in the """"""""3 minute"""""""" intermediate of E441Q RnR and gemcitabine. (4) We plan to determine the alignment of peptides in amyloid fibrils with TOAC labeling. (5) With the development of a 140 GHz gyroamplifier we intend to implement a number of advanced EPR techniques at high field.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002804-20
Application #
7384450
Study Section
Biophysical Chemistry Study Section (BBCB)
Program Officer
Mclaughlin, Alan Charles
Project Start
1987-04-01
Project End
2009-07-14
Budget Start
2008-03-01
Budget End
2009-07-14
Support Year
20
Fiscal Year
2008
Total Cost
$418,519
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
Organized Research Units
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
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
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

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