title: An azide functionalized oligothiophene ligand--a versatile tool for multimodal detection of disease associated protein aggregates.
abstract: Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimer's and Parkinson's disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Leif B G
authors.initials: LBG
authors.lastname: Johansson
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Rozalyn
authors.initials: R
authors.lastname: Simon
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Bergström
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Mikaela
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Prokop
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Carl-Fredrik
authors.initials: CF
authors.lastname: Mandenius
authors.affiliation: Department of Neuropathology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, Berlin 10117, Germany.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Heppner
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden.
authors.forename: Andreas K O
authors.initials: AKO
authors.lastname: Åslund
authors.affiliation: Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping SE-581 83, Sweden. Electronic address: petni@ifm.liu.se.
authors.forename: K Peter R
authors.initials: KPR
authors.lastname: Nilsson
mesh_terms: D001386:Azides / Q000737:chemistry*; D045424:Complex Mixtures; D004867:Equipment Design; D019544:Equipment Failure Analysis; D008024:Ligands; D040081:Protein Array Analysis / Q000295:instrumentation*; D025941:Protein Interaction Mapping / Q000295:instrumentation*; D013050:Spectrometry, Fluorescence / Q000295:instrumentation; D020349:Surface Plasmon Resonance / Q000295:instrumentation; D013876:Thiophenes / Q000737:chemistry*
chemical_list: D001386:Azides; D045424:Complex Mixtures; D008024:Ligands; D013876:Thiophenes
keywords: Click chemistry; Fluorescence; Oligothiophene; Protein aggregates; Surface plasmon resonance