Journal article

Oligopeptides Generated by Neprilysin Degradation of beta-Amyloid Have the Highest Cu(II) Affinity in the Whole A beta Family

Karolina Bossak-Ahmad, Mariusz Mital, Dawid Plonka, Simon C Drew, Wojciech Bal

INORGANIC CHEMISTRY | AMER CHEMICAL SOC | Published : 2019

Abstract

The catabolism of β-amyloid (Aβ) is carried out by numerous endopeptidases including neprilysin, which hydrolyzes peptide bonds preceding positions 4, 10, and 12 to yield Aβ4-9 and a minor Aβ12- x species. Alternative processing of the amyloid precursor protein by β-secretase also generates the Aβ11- x species. All these peptides contain a Xxx-Yyy-His sequence, also known as an ATCUN or NTS motif, making them strong chelators of Cu(II) ions. We synthesized the corresponding peptides, Phe-Arg-His-Asp-Ser-Gly-OH (Aβ4-9), Glu-Val-His-His-Gln-Lys-am (Aβ11-16), Val-His-His-Gln-Lys-am (Aβ12-16), and pGlu-Val-His-His-Gln-Lys-am (pAβ11-16), and investigated their Cu(II) binding properties using pote..

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Grants

Awarded by National Science Centre of Poland


Funding Acknowledgements

The study was sponsored by the National Science Centre of Poland, Grant No. 2014/15/B/ST5/05229 (W.B.). The equipment used was sponsored in part by the Centre for Preclinical Research and Technology (CePT), a project cosponsored by the European Regional Development Fund and Innovative Economy, The National Cohesion Strategy of Poland. S.C.D. was supported by a fellowship awarded by the faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne.