Journal Article

FZJ-2018-03495

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease

Schartmann, E.FZJ* ; Schemmert, S.FZJ* ; Niemietz, N.FZJ* ; Honold, D.FZJ* ; Ziehm, T.FZJ* ; Tusche, M.FZJ* ; Elfgen, A.FZJ* ; Gering, I.FZJ* ; Brener, O.FZJ* ; Shah, N. J.FZJ* ; Langen, K.-J.FZJ* ; Kutzsche, J.FZJ* ; Willbold, D. (Corresponding author)FZJ* ; Willuweit, A. (Corresponding author)FZJ*

2018
IOS Press Amsterdam

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Please use a persistent id in citations: http://hdl.handle.net/2128/19489  doi:10.3233/JAD-180165

Abstract: Diffusible amyloid-β (Aβ) oligomers are currently presumed to be the most cytotoxic Aβ assembly and held responsible to trigger the pathogenesis of Alzheimer’s disease (AD). Thus, Aβ oligomers are a prominent target in AD drug development. Previously, we reported on our solely D-enantiomeric peptide D3 and its derivatives as AD drug candidates. Here, we compare one of the most promising D3 derivatives, ANK6, with its tandem version (tANK6), and its head-to-tail cyclized isoform (cANK6r). In vitro tests investigating the D-peptides’ potencies to inhibit Aβ aggregation, eliminate Aβ oligomers, and reduce Aβ-induced cytotoxicity revealed that all three D-peptides efficiently target Aβ. Subsequent preclinical pharmacokinetic studies of the three all-D-peptides in wildtype mice showed promising blood-brain barrier permeability with cANK6r yielding the highest levels in brain. The peptides’ potencies to lower Aβ toxicity and their remarkable brain/plasma ratios make them promising AD drug candidates.

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)
2. Physik der Medizinischen Bildgebung (INM-4)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2018

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Database coverage:
; ; ; BIOSIS Previews ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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