Journal Article

FZJ-2022-00640

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png All - d - Enantiomeric Peptide D3 Designed for Alzheimer’s Disease Treatment Dynamically Interacts with Membrane-Bound Amyloid-β Precursors

Bocharov, E. V. ; Gremer, L.FZJ* ; Urban, A. S. ; Okhrimenko, I. S. ; Volynsky, P. E. ; Nadezhdin, K. D. ; Bocharova, O. V. ; Kornilov, D. A. ; Zagryadskaya, Y. A. ; Kamynina, A. V. ; Kuzmichev, P. K. ; Kutzsche, J.FZJ* ; Bolakhrif, N.FZJ* ; Müller-Schiffmann, A. ; Dencher, N. A. ; Arseniev, A. S. ; Efremov, R. G. ; Gordeliy, V. I. (Corresponding author)FZJ* ; Willbold, D. (Corresponding author)FZJ*

2021
ACS Washington, DC

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Please use a persistent id in citations: doi:10.1021/acs.jmedchem.1c00632

Abstract: Alzheimer’s disease (AD) is a severe neurodegenerative pathology with no effective treatment known. Toxic amyloid-β peptide (Aβ) oligomers play a crucial role in AD pathogenesis. All-d-Enantiomeric peptide D3 and its derivatives were developed to disassemble and destroy cytotoxic Aβ aggregates. One of the D3-like compounds is approaching phase II clinical trials; however, high-resolution details of its disease-preventing or pharmacological actions are not completely clear. We demonstrate that peptide D3 stabilizing Aβ monomer dynamically interacts with the extracellular juxtamembrane region of a membrane-bound fragment of an amyloid precursor protein containing the Aβ sequence. MD simulations based on NMR measurement results suggest that D3 targets the amyloidogenic region, not compromising its α-helicity and preventing intermolecular hydrogen bonding, thus creating prerequisites for inhibition of early steps of Aβ conversion into β-conformation and its toxic oligomerization. An enhanced understanding of the D3 action molecular mechanism facilitates development of effective AD treatment and prevention strategies.

Note: Kein Post-print vorhanden

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Contributing Institute(s):

1. Strukturbiochemie (IBI-7)

Research Program(s):

1. 5244 - Information Processing in Neuronal Networks (POF4-524) (POF4-524)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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