This title appears in the Scientific Report :
2018
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.
In Vitro Potency and Preclinical Pharmacokinetic Comparison of All-D-Enantiomeric Peptides Developed for the Treatment of Alzheimer’s Disease
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...
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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://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. |