title: Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates.
abstract: Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of Aβ1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimer's diease brain tissue (Aβ plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.
authors: Department of Chemistry, Linköping University, SE-581 83 Linköping, Sweden.
authors: Therése
authors: T
authors: Klingstedt
authors: Andreas
authors: A
authors: Aslund
authors: Rozalyn A
authors: RA
authors: Simon
authors: Leif B G
authors: LB
authors: Johansson
authors: Jeffrey J
authors: JJ
authors: Mason
authors: Sofie
authors: S
authors: Nyström
authors: Per
authors: P
authors: Hammarström
authors: K Peter R
authors: KP
authors: Nilsson
mesh_terms: D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D015335:Molecular Probes / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D011506:Proteins / Q000032:analysis*; D054852:Small Molecule Libraries; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D008024:Ligands; D015335:Molecular Probes; D011506:Proteins; D054852:Small Molecule Libraries; D013876:Thiophenes