Journal Article

FZJ-2015-05663

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Preclinical Pharmacokinetic Studies of the Tritium Labelled D-Enantiomeric Peptide D3 Developed for the Treatment of Alzheimer´s Disease

Jiang, N.FZJ* ; Leithold, L. H. E. ; Post, J.FZJ* ; Ziehm, T.FZJ* ; Mauler, J.FZJ* ; Gremer, L.FZJ* ; Cremer, M.FZJ* ; Schartmann, E.FZJ* ; Shah, N. J.FZJ* ; Kutzsche, J.FZJ* ; Langen, K.-J.FZJ* ; Breitkreutz, J. ; Willbold, D. (Corresponding author)FZJ* ; Willuweit, A. (Corresponding author)FZJ*

2015
PLoS Lawrence, Kan.

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Please use a persistent id in citations: http://hdl.handle.net/2128/9198  doi:10.1371/journal.pone.0128553

Abstract: Targeting toxic amyloid beta (Aβ) oligomers is currently a very attractive drug development strategy for treatment of Alzheimer´s disease. Using mirror-image phage display against Aβ1-42, we have previously identified the fully D-enantiomeric peptide D3, which is able to eliminate Aβ oligomers and has proven therapeutic potential in transgenic Alzheimer´s disease animal models. However, there is little information on the pharmacokinetic behaviour of D-enantiomeric peptides in general. Therefore, we conducted experiments with the tritium labelled D-peptide D3 (3H-D3) in mice with different administration routes to study its distribution in liver, kidney, brain, plasma and gastrointestinal tract, as well as its bioavailability by i.p. and p.o. administration. In addition, we investigated the metabolic stability in liver microsomes, mouse plasma, brain, liver and kidney homogenates, and estimated the plasma protein binding. Based on its high stability and long biological half-life, our pharmacokinetic results support the therapeutic potential of D-peptides in general, with D3 being a new promising drug candidate for Alzheimer´s disease treatment.

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Contributing Institute(s):

1. Strukturelle und funktionelle Organisation des Gehirns (INM-1)
2. Physik der Medizinischen Bildgebung (INM-4)
3. Strukturbiochemie (ICS-6)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2015

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Database coverage:
; ; ; ; BIOSIS Previews ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record

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