# An H/F/X/Y Fast-MAS NMR Probe Particularly for Alzheimer's and Cancer Research

> **NIH NIH R44** · DOTY SCIENTIFIC, INC. · 2020 · $997,231

## Abstract

An H/F/X/Y Fast-MAS NMR Probe Particularly for Alzheimer’s and Cancer Research
Abstract
 More than 20% of current drugs (and a much greater fraction of those in development) are fluorinated
(including such block-busters as Prozac, Lipitor, and Ciprobay). Steady progress over the past decade has
shown magic angle spinning (MAS) solid-state NMR (ssNMR) to be arguably the most powerful analytical tool
for studying macro-molecular structures and their dynamics. For solution NMR, four-channel multinuclear
1H/19F/X/2H probes have recently become more readily available, and such have proven to be extremely
valuable for identification and characterization (using 1H/15N, 19F/13C, and 19F/2H/15N methods) of active
fragments, their binding to soluble proteins, and their effects on such protein-protein interactions. The problem
is that such methods don’t work with insoluble proteins – such as the aggregates and fibrils that are central to
Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and probably even prion-mediated diseases. The
amyloid beta (Aβ) cascade hypothesis is beginning to bring unity to the field of neurodegenerative diseases,
but a key tool for understanding aggregate progression and treatment beyond the stages of the initial seeds
has not been available.
 MAS probes suitable for the needed multi-channel studies of fluorinated drugs and their interactions
have not been available for high-field NMR instruments because of the difficulties of prior rf circuits in handling
close resonances at high frequencies. During the Phase-I, we demonstrated that a novel single-coil circuit
permits, for the first time, efficient high-field H/F/X/Y MAS, with NMR data at 500 MHz and bench experiments
and full-wave detailed modeling at 800 MHz.
 This Phase-II proposal seeks funding to continue the development and testing of high-field H/F/X/Y
fast-MAS probes based on a novel “single-coil” rf circuit optimized for 19F detection with simultaneous
irradiation or detection on any or all of the other channels, and suitable for MAS at fields from 7-28 T, with rotor
diameters from 0.7-3 mm. Analysis suggests that a substantial portion of the spectral line broadening seen in
many MAS experiments is from J-couplings (which is not averaged by MAS) to heteronuclei and spinner-
dependent effects – thermal gradients, axial vibration, and magnetism. The ability to simultaneously decouple
1H, 2H, and 13C or 15N during 19F detection with fast-MAS in a spinner optimized for high resolution with a circuit
and probe design compatible with B0 up to 1200 MHz will permit a dramatic increase in spectral resolution and
sensitivity on, for example, 19F-labeled ligands in amyloid assemblies and their precursor aggregates, or in 19F
labeled DNA-carcinogen adducts.
 The novel probe would allow the powerful suite of NMR acquisition and automated structure
determination protocols developed for solution NMR, which rely mostly on indirect-detected triple- and quad-
resonance schemes, to be su...

## Key facts

- **NIH application ID:** 9908407
- **Project number:** 2R44GM119937-02
- **Recipient organization:** DOTY SCIENTIFIC, INC.
- **Principal Investigator:** Francis DAVID Doty
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $997,231
- **Award type:** 2
- **Project period:** 2016-04-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908407

## Citation

> US National Institutes of Health, RePORTER application 9908407, An H/F/X/Y Fast-MAS NMR Probe Particularly for Alzheimer's and Cancer Research (2R44GM119937-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9908407. Licensed CC0.

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