title: Development of a small D-enantiomeric Alzheimer's amyloid-β binding peptide ligand for future in vivo imaging applications.
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.
authors: Forschungszentrum Jülich, ICS-6, Jülich, Germany.
authors: Susanne Aileen
authors: SA
authors: Funke
authors: Dirk
authors: D
authors: Bartnik
authors: Julian Marius
authors: JM
authors: Glück
authors: Kasia
authors: K
authors: Piorkowska
authors: Katja
authors: K
authors: Wiesehan
authors: Urs
authors: U
authors: Weber
authors: Balazs
authors: B
authors: Gulyas
authors: Christer
authors: C
authors: Halldin
authors: Andrea
authors: A
authors: Pfeifer
authors: Christian
authors: C
authors: Spenger
authors: Andreas
authors: A
authors: Muhs
authors: Dieter
authors: D
authors: Willbold
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D008024:Ligands; D051379:Mice; D016501:Neurites / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; C551352:D1 peptide; D008024:Ligands; D009842:Oligopeptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)