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Article

The Palladium(II) Complex of Aβ4−16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids

1
Institute of Biochemistry and Biophysics, Polish Academy of Sciences, 02-106 Warszawa, Poland
2
NanoBioMedical Centre, Adam Mickiewicz University, 61-614 Poznań, Poland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9200; https://doi.org/10.3390/ijms21239200
Received: 12 November 2020 / Revised: 26 November 2020 / Accepted: 30 November 2020 / Published: 2 December 2020
(This article belongs to the Section Biochemistry)
The Aβ442 peptide is a major beta-amyloid species in the human brain, forming toxic aggregates related to Alzheimer’s Disease. It also strongly chelates Cu(II) at the N-terminal Phe-Arg-His ATCUN motif, as demonstrated in Aβ416 and Aβ49 model peptides. The resulting complex resists ROS generation and exchange processes and may help protect synapses from copper-related oxidative damage. Structural characterization of Cu(II)Aβ4x complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-Aβ416 complex as a model. To avoid a kinetic trapping of Pd(II) in an inappropriate transient structure, we designed an appropriate pH-dependent synthetic procedure for ATCUN Pd(II)Aβ416, controlled by CD, fluorescence and ESI-MS. Its assignments and structure at pH 6.5 were obtained by TOCSY, NOESY, ROESY, 1H-13C HSQC and 1H-15N HSQC NMR experiments, for natural abundance 13C and 15N isotopes, aided by corresponding experiments for Pd(II)-Phe-Arg-His. The square-planar Pd(II)-ATCUN coordination was confirmed, with the rest of the peptide mostly unstructured. The diffusion rates of Aβ416, Pd(II)-Aβ416 and their mixture determined using PGSE-NMR experiment suggested that the Pd(II) complex forms a supramolecular assembly with the apopeptide. These results confirm that Pd(II) substitution enables NMR studies of structural aspects of Cu(II)-Aβ complexes. View Full-Text
Keywords: Alzheimer’s disease; Aβ peptide; NMR spectroscopy; 13C relaxation; Palladium(II); ATCUN motif Alzheimer’s disease; Aβ peptide; NMR spectroscopy; 13C relaxation; Palladium(II); ATCUN motif
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MDPI and ACS Style

Mital, M.; Szutkowski, K.; Bossak-Ahmad, K.; Skrobecki, P.; Drew, S.C.; Poznański, J.; Zhukov, I.; Frączyk, T.; Bal, W. The Palladium(II) Complex of Aβ4−16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids. Int. J. Mol. Sci. 2020, 21, 9200. https://doi.org/10.3390/ijms21239200

AMA Style

Mital M, Szutkowski K, Bossak-Ahmad K, Skrobecki P, Drew SC, Poznański J, Zhukov I, Frączyk T, Bal W. The Palladium(II) Complex of Aβ4−16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids. International Journal of Molecular Sciences. 2020; 21(23):9200. https://doi.org/10.3390/ijms21239200

Chicago/Turabian Style

Mital, Mariusz, Kosma Szutkowski, Karolina Bossak-Ahmad, Piotr Skrobecki, Simon C. Drew, Jarosław Poznański, Igor Zhukov, Tomasz Frączyk, and Wojciech Bal. 2020. "The Palladium(II) Complex of Aβ4−16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids" International Journal of Molecular Sciences 21, no. 23: 9200. https://doi.org/10.3390/ijms21239200

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