Evaluation of Copper(II) Transfer between Amyloid-beta Peptides by Relaxation-Induced Dipolar Modulation Enhancement (RIDME)

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2024
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Hülsmann, Miriam
Godt, Adelheid
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ChemPhysChem. Wiley. 2024, 25(8), e202300928. ISSN 1439-4235. eISSN 1439-7641. Available under: doi: 10.1002/cphc.202300928
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In the brains of Alzheimer's disease patients, fibrillar aggregates containing amyloid-beta (Aβ) peptides are found, along with elevated concentrations of Cu(II) ions. The aggregation pathways of Aβ peptides can be modulated by Cu(II) ions and is determined by the formation and nature of the Cu(II)-Aβ complex. If spin-labeled, the Cu(II)-Aβ complex contains two dipolar coupled paramagnetic centers, the spin label and the Cu(II) ion. Measurement of the dipolar coupling between these paramagnetic centers by relaxation-induced dipolar modulation enhancement (RIDME) allows to monitor the complex formation and thus opens a way to follow the Cu(II) transfer between peptides if a mixture of wild-type and spin-labeled ones is used. We evaluate this approach for a specific Cu(II)-Aβ complex, the aggregation-inert Component II. The kinetics of the Cu(II) transfer can be resolved by performing RIDME in a time-dependent manner. A temporal resolution of seconds has been achieved, with the potential to reach milliseconds, using a rapid-freeze quench device to stop the Cu(II) transfer in solution after defined incubation times.

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ISO 690STEHLE, Juliane, Miriam HÜLSMANN, Adelheid GODT, Malte DRESCHER, Mykhailo AZARKH, 2024. Evaluation of Copper(II) Transfer between Amyloid-beta Peptides by Relaxation-Induced Dipolar Modulation Enhancement (RIDME). In: ChemPhysChem. Wiley. 2024, 25(8), e202300928. ISSN 1439-4235. eISSN 1439-7641. Available under: doi: 10.1002/cphc.202300928
BibTex
@article{Stehle2024-04-16Evalu-69418,
  year={2024},
  doi={10.1002/cphc.202300928},
  title={Evaluation of Copper(II) Transfer between Amyloid-beta Peptides by Relaxation-Induced Dipolar Modulation Enhancement (RIDME)},
  number={8},
  volume={25},
  issn={1439-4235},
  journal={ChemPhysChem},
  author={Stehle, Juliane and Hülsmann, Miriam and Godt, Adelheid and Drescher, Malte and Azarkh, Mykhailo},
  note={Article Number: e202300928}
}
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