Description

• Title:
  The Palladium(II) Complex of A β4-16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids
• Creator:
  Mital, Mariusz;
  Szutkowski, Kosma;
  Bossak‐Ahmad, Karolina;
  Skrobecki, Piotr;
  Drew, Simon;
  Poznański, Jarosław;
  Zhukov, Igor;
  Frączyk, Tomasz;
  Bal, Wojciech
• Description:
  The Aβ4-42 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 Aβ4-16 and Aβ4-9 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)Aβ4-x complexes by NMR would help elucidate their biological function, but is precluded by Cu(II) paramagneticism. Instead we used an isostructural diamagnetic Pd(II)-Aβ4-16 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)Aβ4-16, 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 Aβ4-16, Pd(II)-Aβ4-16 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.
• Object availability:
  free access
• Date:
  2020
• Type:
  Article;
  PeerReviewed
• Language:
  English
• Format:
  application/pdf
• Publisher:
  MDPI
• Relation: http://eprints.ibb.waw.pl/1946 ;https://www.mdpi.com/1422-0067/21/23/9200 ;
  10.3390/ijms21239200
• Subject:
  QD Chemistry;
  QH301 Biology
• Identifier: http://eprints.ibb.waw.pl/1946/1/ijms-21-09200.pdf ;
  Mital, Mariusz and Szutkowski, Kosma and Bossak‐Ahmad, Karolina and Skrobecki, Piotr and Drew, Simon and Poznański, Jarosław and Zhukov, Igor and Frączyk, Tomasz and Bal, Wojciech (2020) The Palladium(II) Complex of A β4-16 as Suitable Model for Structural Studies of Biorelevant Copper(II) Complexes of N-Truncated Beta-Amyloids. International Journal of Molecular Sciences, 21 (23). p. 9200. ISSN 1422-0067
• Data provider:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
• Can I use it?:
  seek permission
• Type:
  other