Research

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· Development and Applications of Novel Solid-State NMR Methods to Study Biomolecules and Materials

· Molecular-Level Understanding of Protein Misfolding for Amyloid Proteins

· Solid-state NMR Analysis of Nano-structure and Supramolecular Structures

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Ongoing projects include

• Development of sensitivity and resolution enhanced solid-state NMR for paramagnetic organometals in non-crystalline solids
• New methods for structural elucidation of biomolecules
• Structural studies of neurodegenerative-disease-related proteins/peptides
• Signal assignments in ¹³C and ¹H NMR of metalloproteins and model systems in solids

Equipments

NMR Lab

• A state-of-the-art 400 MHz triple-resonance Varian Infinitplus solid-state NMR spectrometer
• Varian triple-resonance very-fast MAS probes 3.2 mm
• Home-built triple-resonance very-fast MAS probes 2.5 mm
• Ago Samoson triple-resonance very-fast MAS probes 2.0 mm
• HP network analyzer
• Two SUN work stations
• Agilent digital oscilloscope

Wet Lab

• Two wet labs equipped with various centrifuges
• ABI-433A peptide synthesizer
• A Hitachi 2000 fluorescence spectrometer
• Labconco Class A2 biological safety cabinet
• Waters HPLC system (Shared with Keiderling’s Lab)
• Varian/Carry 300 UV-Vis spectrometer

Major Shared Instruments

• Shared 500 MHz (solid and solution) and 400 MHz Bruker Avance spectrometers for solution NMR
• Shared CD spectrometer, fluorescence, IR spectrometer
• Shared 800, 900 MHz solution-state NMR

What are involved in our research?

• Our research involves a variety of interdisciplinary aspects from analytical chemistry, physical chemistry, inorganic biology, material science, biophysics, and neuroscience. Our students are typically engaged in research projects involving at least two research areas that fit their qualifications.
• We design and perform sophisticated solid-state NMR experiments, based on quantum mechanical calculations and simulations of spin systems.
• We analyze structural and dynamic properties of insoluble neurodegenerative-disease related proteins and peptides, which are major suspects of Alzheimer’s disease and Parkinson’s disease affecting more than 4 million Americans.
• We often perform sample preparations; the techniques used involve biochemical assays, organic synthesis, and analysis by CD, fluorescence, UV/VIS, NMR, and electron microscopy.
• We are establishing ¹³C and ¹H solid-state NMR of paramagnetic organometallics, which has been inaccessible for decades because of its poor sensitivities and resolution. With the methods developed by our group, we speeded up this method by a factor of 2,000 or more.
• We are applying the developed techniques for paramagnetic systems to supramolecular coordination compounds and paramagnetic metallo-proteins.

Research Examples

Structural model of fibrillized Alzheimer’s b-amyloid (Ab) peptides

obtained by solid-state NMR. Since this peptide, which is non-toxic in a monomeric

form gains neurotoxicity in the non-soluble aggregated form, the Ab fibrils have been

suspected as the major cause of Alzheimer’s disease. Although numerous scientists

have been engaged in structural studies of the interesting biomolecules, the structure

obtained by solid-state NMR gives the most detailed structural image to date (ref 17).

2D ¹³C/¹H correlation spectra of non-labeled V(acac)₃ ((a) non CH dipolar filtered

and (b) CH filtered). The CH dipolar filter method greatly helps signal assignments

by selectively removing the signal from CH groups; the three CH peaks at 50-150 ppm

in (a) are removed in (b) peaks are retained. This is the first 2D solid-state NMR spectrum

obtained for non-labeled paramagnetic organometallics. It has been long hopeless

to obtain this kind of 2D high-resolution solid-state NMR spectrum for paramagnetic

organometallics without any isotope enrichments because of notoriously low

sensitivity and resolution (ref 18).