Journal Article

PreJuSER-22156

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Development of a small D-enantiomeric Alzheimer's amyloid-beta binding peptide ligand for future in vivo imaging applications

Funke, S. A.FZJ* ; Bartnik, D.FZJ* ; Glück, J. M.FZJ* ; Pirkowska, K.FZJ* ; Wiesehan, K.FZJ* ; Weber, U.FZJ* ; Gulyas, B.FZJ* ; Halldin, C.FZJ* ; Pfeifer, A.FZJ* ; Spenger, C.FZJ* ; Muhs, A.FZJ* ; Willbold, D.FZJ*

2012
PLoS Lawrence, Kan.

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Please use a persistent id in citations: http://hdl.handle.net/2128/7507  doi:10.1371/journal.pone.0041457

Abstract: Alzheimer's disease (AD) is a devastating disease affecting predominantly the aging population. One of the characteristic pathological hallmarks of AD are neuritic plaques, consisting of amyloid-β peptide (Aβ). While there has been some advancement in diagnostic classification of AD patients according to their clinical severity, no fully reliable method for pre-symptomatic diagnosis of AD is available. To enable such early diagnosis, which will allow the initiation of treatments early in the disease progress, neuroimaging tools are under development, making use of Aβ-binding ligands that can visualize amyloid plaques in the living brain. Here we investigate the properties of a newly designed series of D-enantiomeric peptides which are derivatives of ACI-80, formerly called D1, which was developed to specifically bind aggregated Aβ1-42. We describe ACI-80 derivatives with increased stability and Aβ binding properties, which were characterized using surface plasmon resonance and enzyme-linked immunosorbent assays. The specific interactions of the lead compounds with amyloid plaques were validated by ex vivo immunochemistry in transgenic mouse models of AD. The novel compounds showed increased binding affinity and are promising candidates for further development into in vivo imaging compounds.

Keyword(s): J

Note: Record converted from VDB: 12.11.2012

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Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. Funktion und Dysfunktion des Nervensystems (P33)
2. BioSoft: Makromolekulare Systeme und biologische Informationsverarbeitung (P45)

Appears in the scientific report 2012

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Database coverage:
; ; ; ; BIOSIS Previews ; 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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