Description: In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease

This title appears in the Scientific Report : 2018

In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease

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...

Personal Name(s):	Schartmann, Elena
	Schemmert, Sarah / Niemietz, Nicole / Honold, Dominik / Ziehm, Tamar / Tusche, Markus / Elfgen, Anne / Gering, Ian / Brener, Oleksandr / Shah, Nadim Joni / Langen, Karl-Josef / Kutzsche, Janine / Willbold, Dieter (Corresponding author) / Willuweit, Antje (Corresponding author)
Contributing Institute:	Physik der Medizinischen Bildgebung; INM-4 Strukturbiochemie; ICS-6
Published in:	Journal of Alzheimer's disease, 64 (2018) 3, S. 859 - 873
Imprint:	Amsterdam IOS Press 2018
DOI:	10.3233/JAD-180165
PubMed ID:	29966196
Document Type:	Journal Article
Research Program:	Physical Basis of Diseases
Link:	Get full text OpenAccess OpenAccess
	Publikationsportal JuSER

Please use the identifier: http://dx.doi.org/10.3233/JAD-180165 in citations.
Please use the identifier: http://hdl.handle.net/2128/19489 in citations.

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.