%0 Journal Article %J J Alzheimers Dis %D 2018 %T In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer's Disease. %A Schartmann, Elena %A Schemmert, Sarah %A Niemietz, Nicole %A Honold, Dominik %A Ziehm, Tamar %A Tusche, Markus %A Elfgen, Anne %A Gering, Ian %A Brener, Oleksandr %A Shah, Nadim Joni %A Langen, Karl-Josef %A Kutzsche, Janine %A Willbold, Dieter %A Willuweit, Antje %X

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.

%B J Alzheimers Dis %V 64 %P 859-873 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/29966196?dopt=Abstract %R 10.3233/JAD-180165