Hydrogen Bonding in Alzheimer’s Amyloid‐β Fibrils Probed by <sup>15</sup>N{<sup>17</sup>O} REAPDOR Solid‐State NMR Spectroscopy

Antzutkin, Oleg N.; Iuga, Dinu; Филиппов, А. В.; Kelly, Robert; Becker‐Baldus, Johanna; Brown, Steven P.; Dupree, R.

doi:10.1002/anie.201203595

Cited by 43 publications

(33 citation statements)

References 37 publications

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“…[1] Over the years, 17 O NMR spectroscopy has actually progressively emerged as a unique tool for studying the structure, properties and reactivity of many systems, [2][3][4] ranging from peptides and enzyme active sites to catalysts, batteries, glasses, and molecular co-crystals, just to name a few. [5] Indeed, the chemical shift range of 17 O exceeds 1500 ppm, and in the case of solids, the other 17 O NMR parameters (chemical shift anisotropy and quadrupolar tensors) can also provide important information concerning its local environment.…”

Section: O Solid State Nmr Applications Is Demonstratedmentioning

confidence: 99%

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

et al. 2017

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17O NMR spectroscopy has been the subject of vivid interest in recent years, because there is increasing evidence that it can provide unique insight into the structure and reactivity of many molecules and materials. However, due to the very poor natural abundance of oxygen‐17, 17O labeling is generally a prerequisite. This is a real obstacle for most research groups, because of the high costs and/or strong experimental constraints of the most frequently used 17O‐labeling schemes. Here, we show for the first time that mechanosynthesis offers unique opportunities for enriching in 17O a variety of organic and inorganic precursors of synthetic interest. The protocols are fast, user‐friendly, and low‐cost, which makes them highly attractive for a broad research community, and their suitability for 17O solid‐state NMR applications is demonstrated.

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Section: O Solid State Nmr Applications Is Demonstratedmentioning

confidence: 99%

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

et al. 2017

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“…Specifically, 17 O MAS NMR spectra typically display residual second-order broadening not averaged to zero by MAS. 10,11 Modest sensitivity gains for studying 17 O NMR have been achieved in the past by using isotopic enrichment 12–15 , performing the experiments in magnetic fields greater than 16.4 T 16–20 , and applying population transfer techniques. 21,22 Recently dynamic nuclear polarization (DNP) of 17 O has provided effective gains in sensitivity in a series of biological and inorganic chemical systems.…”

Section: Introductionmentioning

confidence: 99%

Structural Insights into Bound Water in Crystalline Amino Acids: Experimental and Theoretical ¹⁷O NMR

et al. 2015

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Direct 17O NMR structural studies of bound water in crystalline hydrates and biological macromolecules are challenging due to the low natural abundance and quadrupolar nature of 17O nuclei. However, the advent of high field NMR positions 17O NMR to become an important tool to address structural problems in biological solids. We show herein that the NMR properties of 17O in a series of amino acids and dipeptides can be determined by a combination of non-spinning and magic-angle spinning experiments using a range of magnetic field strengths from 9.4 to 21.1 T. Furthermore, we propose a 17O chemical shift fingerprint region for bound water molecules in biological solids that is well outside the previously determined ranges for carbonyl, carboxylic, and hydroxyl oxygens, thereby offering the ability to resolve multiple 17O environments using rapid one-dimensional NMR techniques. Finally, we compare our experimental data against quantum chemical calculations using GIPAW and hybrid-DFT, finding intriguing discrepancies between the electric field gradients calculated from structures determined by x-ray and neutron diffraction.

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“…The presence of these additional five residues in the N-terminal region of the full-sized parallel fibril increases further the differences in stability between the two forms but is not accounted for in our simulations. Another important factor in stabilizing the supramolecular organization of amyloid peptides 44 is the arrangement of hydrogen bonds. We have analyzed the extent of hydrogen bonds in order to determine whether there is a difference between parallel or anti-parallel β-sheet organizations of the wild type and Iowa mutant oligomers.…”

Section: Structural Stability Of Wild Type and Iowa Mutant Aggregatesmentioning

confidence: 99%

Stability of Iowa mutant and wild type Aβ-peptide aggregates

Alred

Scheele

Berhanu

et al. 2014

The Journal of Chemical Physics

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Recent experiments indicate a connection between the structure of amyloid aggregates and their cytotoxicity as related to neurodegenerative diseases. Of particular interest is the Iowa Mutant, which causes early-onset of Alzheimer's disease. While wild-type Amyloid β-peptides form only parallel beta-sheet aggregates, the mutant also forms meta-stable antiparallel beta sheets. Since these structural variations may cause the difference in the pathological effects of the two Aβ-peptides, we have studied in silico the relative stability of the wild type and Iowa mutant in both parallel and antiparallel forms. We compare regular molecular dynamics simulations with such where the viscosity of the samples is reduced, which, we show, leads to higher sampling efficiency. By analyzing and comparing these four sets of all-atom molecular dynamics simulations, we probe the role of the various factors that could lead to the structural differences. Our analysis indicates that the parallel forms of both wild type and Iowa mutant aggregates are stable, while the antiparallel aggregates are meta-stable for the Iowa mutant and not stable for the wild type. The differences result from the direct alignment of hydrophobic interactions in the in-register parallel oligomers, making them more stable than the antiparallel aggregates. The slightly higher thermodynamic stability of the Iowa mutant fibril-like oligomers in its parallel organization over that in antiparallel form is supported by previous experimental measurements showing slow inter-conversion of antiparallel aggregates into parallel ones. Knowledge of the mechanism that selects between parallel and antiparallel conformations and determines their relative stability may open new avenues for the development of therapies targeting familial forms of early-onset Alzheimer's disease. © 2014 AIP Publishing LLC.

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Hydrogen Bonding in Alzheimer’s Amyloid‐β Fibrils Probed by ¹⁵N{¹⁷O} REAPDOR Solid‐State NMR Spectroscopy

Cited by 43 publications

References 37 publications

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

Structural Insights into Bound Water in Crystalline Amino Acids: Experimental and Theoretical ¹⁷O NMR

Stability of Iowa mutant and wild type Aβ-peptide aggregates

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Hydrogen Bonding in Alzheimer’s Amyloid‐β Fibrils Probed by 15N{17O} REAPDOR Solid‐State NMR Spectroscopy

Cited by 43 publications

References 37 publications

Unleashing the Potential of 17O NMR Spectroscopy Using Mechanochemistry

Unleashing the Potential of 17O NMR Spectroscopy Using Mechanochemistry

Structural Insights into Bound Water in Crystalline Amino Acids: Experimental and Theoretical 17O NMR

Stability of Iowa mutant and wild type Aβ-peptide aggregates

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Hydrogen Bonding in Alzheimer’s Amyloid‐β Fibrils Probed by ¹⁵N{¹⁷O} REAPDOR Solid‐State NMR Spectroscopy

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

Unleashing the Potential of ¹⁷O NMR Spectroscopy Using Mechanochemistry

Structural Insights into Bound Water in Crystalline Amino Acids: Experimental and Theoretical ¹⁷O NMR