Sensitivity-Enhanced Solid-State NMR Detection of Structural Differences and Unique Polymorphs in Pico- to Nanomolar Amounts of Brain-Derived and Synthetic 42-Residue Amyloid-β Fibrils.

Amyloid-β (Aβ) fibrils in neuritic plaques are a hallmark of Alzheimer's disease (AD). Since the 42-residue Aβ (Aβ42) fibril is the most pathogenic among different Aβ species, its structural characterization is crucial to our understanding of AD. While several polymorphs have been reported for Aβ40, previous studies of Aβ42 fibrils prepared at neutral pH detected essentially only one structure, with an S-shaped β-sheet arrangement (, Xiao et al.

Progress in proton-detected solid-state NMR (SSNMR): Super-fast 2D SSNMR collection for nano-mole-scale proteins.

Proton-detected solid-state NMR (SSNMR) spectroscopy has attracted much attention due to its excellent sensitivity and effectiveness in the analysis of trace amounts of amyloid proteins and other important biological systems. In this perspective article, we present the recent sensitivity limit of H-detected SSNMR using "ultra-fast" magic-angle spinning (MAS) at a spinning rate (ν) of 80-100 kHz. It was demonstrated that the high sensitivity of H-detected SSNMR at ν of 100 kHz and fast recycling using the paramagnetic-assisted condensed data collection (PACC) approach permitted "super-fast" collection of H-detected 2D protein SSNMR.

Evolution of CPMAS under fast magic-angle-spinning at 100 kHz and beyond.

This article describes recent trends of high-field solid-state NMR (SSNMR) experiments for small organic molecules and biomolecules using (13)C and (15)N CPMAS under ultra-fast MAS at a spinning speed (νR) of 80-100kHz. First, we illustrate major differences between a modern low-power RF scheme using UFMAS in an ultra-high field and a traditional CPMAS scheme using a moderate sample spinning in a lower field. Features and sensitivity advantage of a low-power RF scheme using UFMAS and a small sample coil are summarized for CPMAS-based experiments.