title: Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures.
abstract: Alzheimer's disease (AD) is characterized by the self-assembly of amyloid beta (Aβ) peptides. Recent models implicate some of the earliest Aβ oligomers, such as trimers and tetramers, in disease. However, the roles of these structures remain uncertain, in part, because selective probes of their formation are not available. Toward that goal, we generated bivalent versions of the known Aβ ligand, the pentapeptide KLVFF. We found that compounds containing sufficiently long linkers (∼19 to 24 Å) recognized primarily Aβ trimers and tetramers, with little binding to either monomer or higher order structures. These compounds might be useful probes for early Aβ oligomers.
authors.affiliation: Department of Biological Chemistry, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, Michigan 48109-2216, United States.
authors.forename: Ashley A
authors.initials: AA
authors.lastname: Reinke
authors.forename: Peter M U
authors.initials: PM
authors.lastname: Ung
authors.forename: Jerome J
authors.initials: JJ
authors.lastname: Quintero
authors.forename: Heather A
authors.initials: HA
authors.lastname: Carlson
authors.forename: Jason E
authors.initials: JE
authors.lastname: Gestwicki
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics*; D008024:Ligands; D015335:Molecular Probes / Q000737:chemistry / Q000235:genetics; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics*
chemical_list: D016229:Amyloid beta-Peptides; D008024:Ligands; D015335:Molecular Probes; D010446:Peptide Fragments; C529399:amyloid beta-protein (16-20)