During the past year we published the initial low resolution structure of a peptide derived from b-amyloid, the protein thought to cause Alzheimer's disease. Several important advances have been made in dipolar recoupling in magic angle spinning (MAS) spectra, so that it is possible to perform spectral assignments and measure internuclear distances in solid biological materials in a general manner. Multiple quantum NMR techniques for observing high resolution spectra of quadrupolar nuclei have been demonstrated. The importance of these experiments is that in principle they enable observation of high resolution isotropic spectra of ~70% of the periodic table which has I>=3/2. These experiments will function optimally at high magnetic fields. We have developed new techniques for decoupling solids which yield increases in resolution of ~5-10 depending on the samples. Despite several intense research in this and in other laboratories, this is the first significant improvement in decoupling since the introduction of high resolution solid state NMR ~25 years ago. In addition, we have developed an approach to dynamically polarize protein solutions resulting in enhancements in signal strengths by factors of up to 185. The approach utilizes the gyrotron oscillator developed in collaboration with the MIT Plasma Fusion Center and DNP/NMR spectrometer we have assembled. It appears to be generally applicable.
High frequency 140 GHz EPR has also proven to be a valuable tool in the investigation of inhibition of protein free radicals. We have concentrated on two inhibitors of ribonucleotide reductase and demonstrated that an azide inhibitor results in the formation of a Cys-N[Sigma] radical and a difluoromethylene inhibitor yields an allyl radical.
High field solution NMR experiments were employed to determine the structure of the complex between peptides from the HIV Rev protein and the Rev-Responsive Element (RRE) RNA. The primary tool in this work was multidimensional heteronuclear NMR. This structure provided insight into the manner of RNA-protein recognition, which is an important problem in structural biology, as well as information which could prove helpful for design of novel therapeutic strategies for HIV.
NMR microscopy research was focused on the application of radiofrequency field gradients to improve the efficiency of solution NMR experiments, which in turn will improve the efficiency of studies of the structure and dynamics of large molecules. Recently the area of radiation damping and how to avoid it have been addressed and mechanisms discovered whereby damping can be initiated by a noise source and quenched by introduction of an effective field which couples the transverse and longitudinal components of magnetization.
The condensed matter physics effort at the FBML is focused on spin-dependent tunneling between magnetic films of CrO2. The films have potential applications in the digital electronics industry, automobiles and medical diagnostics. In addition, the Stark-Faraday effect in GaAs-AlGaAs structures at 0.8um has been observed. The effect has possible optoelectronic device applications.
The Magnet Technology group completed the winding of the major part of the 45T hybrid magnet to be installed at the National High Magnetic Field Laboratory in Tallahassee. In addition, the past year has seen the acquisition of five new magnets for the magnetic resonance research effort. These include a 104 mm, 500 MHz magnet for solid state spectroscopy, a 52 mm, 600 MHz magnet and spectrometer for microscopy and a similar system for solution NMR, and a 62 mm, 750 MHz magnet for solution and solid state experiments Finally, we have acquired a 125 mm 5T magnet with a sweep coil for extended high field EPR experiments.
The Laboratory contributes to undergraduate education by participation in the Undergraduate Research Opportunities Program (UROP) a program that encourages and supports research-based intellectual collaborations of MIT undergraduates with Institute faculty and research staff. In addition the laboratory has 35 full time graduate and 10 postdoctoral students who are performing research.
Plans are continuing for a major expansion of MRI activities involving the Harvard/MIT Division of Health Sciences and Technology (HST). HST is in the process of recruiting senior faculty members in the area of functional MRI, and the FBML Director is working closely with HST faculty toward the recruitment of renowned individuals in this field.
A comprehensive proposal submitted in 1995 awaits action by the NSF. If the proposal is funded the Operations group previously employed at the Laboratory would be rehired along with several new hires. The motor-generators would be replaced by a thyristor power supply and new magnets would be built to reach 40 T.
A proposal to the NIH for the development of very high field, wide bore NMR magnets also awaits a decision. If funded, the Technology Group would pursue the program for three years.
Robert G. Griffin
John E.C. Williams
MIT Reports to the President 1995-96