liu.seSearch for publications in DiVA
Endre søk
Begrens søket
1 - 22 of 22
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Arja, Katriann
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan. Linköping, .
    Sjölander, Daniel
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Åslund, Alma
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Prokop, Stefan
    Charite, Germany .
    Heppner, Frank L.
    Charite, Germany .
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Lindgren, Mikael
    Norwegian University of Science and Technology, Norway .
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten. Linköping, .
    Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand2013Inngår i: Macromolecular rapid communications, ISSN 1022-1336, E-ISSN 1521-3927, Vol. 34, nr 9, s. 723-730Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Fluorescent probes identifying protein aggregates are of great interest, as deposition of aggregated proteins is associated with many devastating diseases. Here, we report that a fluorescent amyloid ligand composed of two distinct molecular moieties, an amyloidophilic pentameric oligothiophene and a porphyrin, can be utilized for spectral and lifetime imaging assessment of recombinant A 1-42 amyloid fibrils and A deposits in brain tissue sections from a transgenic mouse model with Alzheimers disease pathology. The enhanced spectral range and distinct lifetime diversity of this novel oligothiopheneporphyrin-based ligand allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye.

  • 2.
    Aslund, Andreas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Fluorescent oligo and poly-thiophenes and their utilization for recording biological events of diverse origin-when organic chemistry meets biology.2009Inngår i: Journal of chemical biology, ISSN 1864-6166, Vol. 2, nr 4, s. 161-175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The technique of using luminescent oligo-thiophenes and luminescent conjugated poly-thiophenes to monitor biological processes has gained increased interest from scientists within different research areas, ranging from organic chemistry and photo-physics to biology since its introduction. The technique is generally straightforward and requires only standard equipment, and the result is available within minutes from sample preparation. In this review, the syntheses of oligo and polythiophenes developed over the last decades are discussed. Furthermore, the utilization of these molecular agents for exploring biological events, e.g., DNA hybridization or protein misfolding events, are covered.

  • 3.
    Hammarström, Per
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    A Fluorescent Pentameric Thiophene Derivative Detects in Vitro-Formed Prefibrillar Protein Aggregates2010Inngår i: BIOCHEMISTRY, ISSN 0006-2960, Vol. 49, nr 32, s. 6838-6845Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of their likely role in the mechanism of fibril formation and because of the growing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. Herein, we explore the use of an anionic oligothiophene derivative, p-FTAA, for detection of prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins (insulin, lysozyme, and prion protein). p-FTAA generally detected prefibrillar protein aggregates that could not be detected by thioflavine T fluorescence and in addition showed high fluorescence when bound to mature fibrils. Second, the kinetics of protein aggregation or the formation of amyloid fibrils of insulin was not extensively influenced by the presence of various concentrations of p-FTAA. These results establish the use of p-FTAA as an additional tool for studying the process of protein aggregation.

  • 4.
    Heilbronner, Goetz
    et al.
    University of Tubingen, Germany .
    Eisele, Yvonne S.
    University of Tubingen, Germany .
    Langer, Franziska
    University of Tubingen, Germany .
    Kaeser, Stephan A.
    University of Tubingen, Germany .
    Novotny, Renata
    University of Tubingen, Germany .
    Nagarathinam, Amudha
    University of Tubingen, Germany .
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Jucker, Mathias
    University of Tubingen, Germany .
    Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice2013Inngår i: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 14, nr 11, s. 1017-1022Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The polymorphic beta-amyloid lesions present in individuals with Alzheimers disease are collectively known as cerebral beta-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop beta-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and A beta 40/A beta 42 peptide ratio. To determine the nature of such beta-amyloid morphotypes, beta-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced beta-amyloid deposition with the morphological, conformational, and A beta 40/A beta 42 ratio characteristics of beta-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced b-amyloid deposits with the characteristics of beta-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced beta-amyloid deposits, although less prominent, and the induced deposits were similar to the beta-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated A beta in APP transgenic mice can be maintained by seeded conversion.

  • 5.
    Herrmann, Uli S.
    et al.
    University of Zurich Hospital, Switzerland.
    Schuetz, Anne K.
    ETH, Switzerland.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Huang, Danzhi
    University of Zurich, Switzerland.
    Saban, Dino
    University of Zurich Hospital, Switzerland.
    Nuvolone, Mario
    University of Zurich Hospital, Switzerland.
    Li, Bei
    University of Zurich Hospital, Switzerland.
    Ballmer, Boris
    University of Zurich Hospital, Switzerland.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Mason, Jeffrey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Rushing, Elisabeth
    University of Zurich Hospital, Switzerland.
    Budka, Herbert
    University of Zurich Hospital, Switzerland.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Boeckmann, Anja
    University of Lyon 1, France.
    Caflisch, Amedeo
    University of Zurich, Switzerland.
    Meier, Beat H.
    ETH, Switzerland.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Hornemann, Simone
    University of Zurich Hospital, Switzerland.
    Aguzzi, Adriano
    University of Zurich Hospital, Switzerland.
    Structure-based drug design identifies polythiophenes as antiprion compounds2015Inngår i: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 7, nr 299, s. 299ra123-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrPSc, a misfolded and aggregated form of the cellular prion protein (PrPC). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by greater than80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.

  • 6.
    Johansson, Leif B. G.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Bergström, Gunnar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teknisk biologi. Linköpings universitet, Tekniska högskolan.
    Eriksson, Mikaela
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Prokop, Stefan
    Charite, Germany.
    Mandenius, Carl-Fredrik
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Teknisk biologi. Linköpings universitet, Tekniska högskolan.
    Heppner, Frank L.
    Charite, Germany.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates2015Inngår i: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 63, s. 204-211Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons 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.

  • 7.
    Karlsson, Roger H.
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi. Linköpings universitet, Tekniska högskolan.
    Herland, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Hamedi, Mahiar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Iron Catalyzed Polymerization of Alkoxysulfonate-Functionalized EDOT gives2007Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002Artikkel i tidsskrift (Fagfellevurdert)
  • 8.
    Karlsson, Roger
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Herland, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Hamedi, Mahiar
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Wigenius, Jens
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Liu, Xianjie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ytors Fysik och Kemi. Linköpings universitet, Tekniska högskolan.
    Fahlman, Mats
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Ytors Fysik och Kemi. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Iron-Catalyzed Polymerization of Alkoxysulfonate-Functionalized 3,4-Ethylenedioxythiophene Gives Water-Soluble Poly(3,4-ethylenedioxythiophene) of High Conductivity2009Inngår i: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 21, nr 9, s. 1815-1821Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chemical polymerization of a 3,4-ethylenedioxythiophene derivative bearing a sulfonate group (EDOTS) is reported. The polymer, PEDOT-S, is fully water-soluble and has been produced by polymerizing EDOT-S in water, using Na2S2O8 and a catalytic amount of FeCl3. Elemental analysis and XPS measurements indicate that PEDOT-S is a material with a substantial degree of self-doping, but also contains free sulfate ions as charge-balancing counterions of the oxidized polymer. Apart from self-doping PEDOT-S, the side chains enable full water solubility of the material; DLS studies show an average cluster size of only 2 nm. Importantly, the solvation properties of the PEDOT-S are reflected in spin-coated films, which show a surface roughness of 1.2 nm and good conductivity (12 S/cm) in ambient conditions. The electro-optical properties of this material are shown with cyclic voltammetry and spectroelectrochemical experiment reveals an electrochromic contrast (similar to 48% at lambda(max) = 606 nm).

  • 9.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Cairns, Nigel J.
    Washington University, MO USA .
    Sigurdson, Christina J.
    University of Calif San Diego, CA USA .
    Goedert, Michel
    MRC, England .
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    The Structural Basis for Optimal Performance of Oligothiophene-Based Fluorescent Amyloid Ligands: Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates2013Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, nr 31, s. 10179-10192Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates.

  • 10.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, K. O. Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Cairns, Nigel J.
    Department of Neurology, Alzheimer’s Disease Research Center, Washington University St. Louis, United States.
    Sigurdson, Christina J.
    Department of Pathology, University of California, San Diego, La Jolla, California, United States.
    Goedert, Michel
    MRC Laboratory of Molecular Biology Hills Road, Cambridge, UK.
    Nilsson, K. Peter R.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    The structural basis for optimal performance of oligothiophene based fluorescent amyloid ligands: Conformational flexibility is essential for spectral assignment of a diversity of protein aggregatesManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Protein misfolding diseases are characterized by deposition of protein aggregates and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as Thioflavin T (ThT) and Congo red. Herein, the molecular requirements for achieving LCOs able to detect non-thioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by i) replacing thiophene units with selenophene or phenylene moieties or ii) alternating the anionic substituents along the  thiophene backbone. In addition, two asymmetric tetrameric ligands were  generated. Overall, the results from this study identified conformational  freedom and extended conjugation of the conjugated backbone as crucial  determinants for obtaining superior thiophene-based optical ligands for  sensitive detection and spectral assignment of diseaseassociated protein aggregates.

  • 11.
    Klingstedt, Therése
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Johansson, Leif B. G.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Mason, Jeffrey
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Proteinkemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates2011Inngår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 24, s. 8356-8370Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    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 A beta 1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimers diease brain tissue (A beta 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.

  • 12.
    Li, Feng
    et al.
    Wageningen University.
    Martens, Aernout A
    Wageningen University.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    de Wolf, Frits A
    Wageningen University.
    Cohen Stuart, Martien A
    Wageningen University.
    Sudholter, Ernst J R
    Delft University Technology.
    Marcelis, Antonius T M
    Wageningen University.
    Leermakers , Frans A M
    Wageningen University.
    Formation of nanotapes by co-assembly of triblock peptide copolymers and polythiophenes in aqueous solution2009Inngår i: SOFT MATTER, ISSN 1744-683X , Vol. 5, nr 8, s. 1668-1673Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Nanotapes are formed by the co-assembly of triblock peptide copolymers with an amino acid-substituted polythiophene derivative (PTT). The driving force for the assembly is ionic interaction (complex coacervation). These nanotapes were visualized by atomic force microscopy and confocal laser scanning microscopy. The interactions between the triblock peptide copolymers and the PTT are also expressed in the steady state and time resolved fluorescence spectra. The steady-state spectra indicate that upon interaction with the peptide copolymer, the backbone of the PTT adopts a rather twisted, and definitely less, aggregated conformation. The time-resolved fluorescence decay studies further confirm this interpretation. The structure of these nanotapes at the mesoscopic scale depends, among other physical chemical parameters, on the concentrations of its constituents.

  • 13.
    Li, Feng
    et al.
    Wageningen University.
    Palaniswamy, Ganesan
    Wageningen University.
    de Jong, Menno R.
    Biomade Technol Fdn.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Marcelis, Antonius T. M.
    Wageningen University.
    Sudholter, Ernst J. R.
    Delft University of Technology.
    Cohen Stuart, Martien A.
    Wageningen University.
    Leermakers, Frans A. M.
    Wageningen University.
    Nanowires Formed by the Co-Assembly of a Negatively Charged Low-Molecular Weight Gelator and a Zwitterionic Polythiophene2010Inngår i: ChemPhysChem, ISSN 1439-4235, E-ISSN 1439-7641, Vol. 11, nr 9, s. 1956-1960Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Conjugated organic nanowires have been prepared by co-assembling a carboxylate containing low-molecular weight gelator (LMWG) and an amino acid substituted polythiophene derivative (PTT). Upon introducing the zwitterionic polyelectrolyte PTT to a basic molecular solution of the organogelator, the negative charges on the LMWG are compensated by the positive charges of the PTT. As a result, nanowires form through co-assembly. These nanowires are visualized by both transmission electron microscopy (TEM) and atomic force microscopy (AFM). Depending on the concentration and ratio of the components these nanowires can be micrometers long. These measurements further suggest that the aggregates adopt a helical conformation. The morphology of these nanowires are studied with fluorescent confocal laser scanning microscopy (CLSM). The interactions between LMWG and PTT are characterized by steady-state and time-resolved fluorescence spectroscopy studies. The steady-state spectra indicate that the backbone of the PTT adopts a more planar and more aggregated conformation when interacting with LMWG. The time-resolved fluorescence decay studies confirm this interpretation.

  • 14.
    Lindgren, M.
    et al.
    Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
    Glimsdal, E.
    Department of Physics, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Simon, Rozalyn
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska fakulteten.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Luminescence and two-photon absorption cross section of novel oligomeric luminescent conjugated polythiophenes for diagnostics of amyloid fibrils2010Inngår i: Nonlinear Optics Quantum Optics, ISSN 1543-0537, Vol. 40, nr 1-4, s. 241-251Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Here we present the TPA cross section and quantum efficiencies of a series of novel oligomeric luminescent conjugated polythiophenes used for detection and spectral diagnostics of amyloid protein aggregates of the amyloid-beta peptide associated with Alzheimers disease. Specifically, these probes consist of pentameric or heptameric thiophenes derivatives with carboxylic substituents attached onto various thiophene rings. The probes absorbs over a broad range approx. 400-500 nm with quantum efficiency of approx. 20% in at neutral pH conditions, and also showed TPA cross sections of 5-50 GM in the range 700-840 nm, in the same order of magnitude as commonly used fluorescein derivatives. Importantly, the multiphoton excitation capabilities of LCPs provided excellent performance when compared to imaging using conventional "single photon" excitation. It is also demonstrated their utilization in both one-and two-photon excitation laser scanning microscope spectral imaging for diagnostics of Alzheimer disease pathology in ex vivo histological sections.

  • 15.
    Margalith, Ilan
    et al.
    University of Zurich Hospital, Switzerland .
    Suter, Carlo
    University of Zurich Hospital, Switzerland .
    Ballmer, Boris
    University of Zurich Hospital, Switzerland .
    Schwarz, Petra
    University of Zurich Hospital, Switzerland .
    Tiberi, Cinzia
    University of Zurich Hospital, Switzerland .
    Sonati, Tiziana
    University of Zurich Hospital, Switzerland .
    Falsig, Jeppe
    University of Zurich Hospital, Switzerland .
    Nyström, Sofie
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Yam, Alice
    Novartis Diagnost, USA .
    Whitters, Eric
    Novartis Diagnost, USA .
    Hornemann, Simone
    University of Zurich Hospital, Switzerland .
    Aguzzi, Adriano
    University of Zurich Hospital, Switzerland .
    Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates2012Inngår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, nr 23, s. 18872-18887Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.

  • 16.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Ikenberg, Kristian
    University Hospital of Zurich.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Fransson, Sophia
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Röcken, Christoph
    Christian-Albrechts-University, Kiel.
    Moch, Holger
    University Hospital of Zurich.
    Aguzzi, Adriano
    University Hospital of Zurich.
    Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy.2010Inngår i: The American journal of pathology, ISSN 1525-2191, Vol. 176, nr 2, s. 563-574Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.

  • 17.
    Nilsson, Peter
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, Andreas
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi.
    Berg, Ina
    Nyström, Sofie
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi.
    Konradsson, Peter
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi.
    Herland, Anna
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Inganäs, Olle
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik.
    Stabo-Eeg, Frantz
    Lindgren, Mikael
    Westermark, Gunilla
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Avdelningen för medicinsk cellbiologi.
    Lannfelt, Lars
    Nilsson, Lars N G
    Hammarström, Per
    Linköpings universitet, Tekniska högskolan. Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi.
    Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes2007Inngår i: ACS Chemical Biology, ISSN 1554-8929, Vol. 2, nr 8, s. 553-560Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.

  • 18.
    Simon, Rozalyn
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Shirani, Hamid
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Åslund, K. O. Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Bäck, Marcus
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Haroutunian, Vahram
    Department of Psychiatry and Alzheimer’s Disease Research Center, Mount Sinai School of Medicine, New York, USA.
    Gandy, Sam
    Department of Psychiatry and Alzheimer’s Disease Research Center, Mount Sinai School of Medicine, New York, USA.
    Nilsson, Peter R
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska högskolan.
    Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts2014Inngår i: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, nr 39, s. 12537-12543Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have proven useful for spectral discrimination of amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer’s disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Aβ and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Aβ and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates.

  • 19.
    Åslund, Andreas
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Designing thiophene-based fluorescent probes for the study of neurodegenerative protein aggregation diseases: From test tube to in vivo experiments2009Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Protein aggregation is an event related to numerous neurodegenerative diseases, such as Alzhemier’s disease and prion diseases. However little is known as to how and why the aggregates form and furthermore, the toxic specie may not be the mature fibril but an on route or off route specie towards mature aggregates. During this project molecular probes were synthesized that may shed some light to these questions. The probes are thiophene based and the technique used for detection was mainly fluorescence. It was shown that the previously established thiophene based in vitro staining technique is valid ex vivo and in vivo. This would not have been possible without the synthesis of a variety of functionalized polymeric thiophene based probes; their in vitro and ex vivo staining properties were taken into consideration when the design of the small oligomeric probes were decided upon. These probes were shown to spectrally distinguish different types of amyloid, pass the bloodbrain barrier within minutes and specifically and selectively stain protein aggregates in the brains of mice.

    Delarbeid
    1. Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
    Åpne denne publikasjonen i ny fane eller vindu >>Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
    Vise andre…
    2007 (engelsk)Inngår i: ACS Chemical Biology, ISSN 1554-8929, Vol. 2, nr 8, s. 553-560Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-40622 (URN)10.1021/cb700116u (DOI)53662 (Lokal ID)53662 (Arkivnummer)53662 (OAI)
    Tilgjengelig fra: 2009-10-10 Laget: 2009-10-10 Sist oppdatert: 2019-11-08
    2. Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states
    Åpne denne publikasjonen i ny fane eller vindu >>Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states
    Vise andre…
    2007 (engelsk)Inngår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 18, nr 6, s. 1860-1868Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Improved probes for amyloid fibril formation are advantageous for the early detection and better understanding of this disease-associated process. Here, we report a comparative study of eight luminescent conjugated polythiophene derivates (LCPs) and their discrimination of a protein (insulin) in the native or amyloid-like fibrillar state. For two of the LCPs, the synthesis is reported. Compared to their monomer-based analogues, trimer-based LCPs showed significantly better optical signal specificity for amyloid-like fibrils, seen from increased quantum yield and spectral shift. The trimer-based LCPs alone were highly quenched and showed little interaction with native insulin, as seen from analytical ultracentrifugation and insignificant spectral differences from the trimer-based LCP in buffered and native protein solution. Hence, the trimer-based LCPs showed enhanced discrimination between the amyloid-like fibrillar state and the corresponding native protein.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14600 (URN)10.1021/bc700180g (DOI)
    Tilgjengelig fra: 2007-10-12 Laget: 2007-10-12 Sist oppdatert: 2018-04-25
    3. Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses
    Åpne denne publikasjonen i ny fane eller vindu >>Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses
    Vise andre…
    2009 (engelsk)Inngår i: ACS CHEMICAL BIOLOGY, ISSN 1554-8929, Vol. 4, nr 8, s. 673-684Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Molecular probes for selective Identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two, mouse-adapted prion strains. p-FTAA also revealed a transient soluble pre-fibrillar non-thioflavinophilic A beta-assemblies during in vitro fibrillation of A beta peptides. In brain tissue samples, A beta deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localliation with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual A beta plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimers disease, namely, A beta aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, A beta-tau interactions, and pathogenesis both ex vivo and in vivo.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-20420 (URN)10.1021/cb900112v (DOI)
    Tilgjengelig fra: 2009-09-08 Laget: 2009-09-07 Sist oppdatert: 2018-04-25
  • 20.
    Åslund, Andreas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Herland, Anna
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Jonsson, Bengt-Harald
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär Bioteknik. Linköpings universitet, Tekniska högskolan.
    Inganäs, Olle
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biomolekylär och Organisk Elektronik. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states2007Inngår i: Bioconjugate chemistry, ISSN 1043-1802, E-ISSN 1520-4812, Vol. 18, nr 6, s. 1860-1868Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Improved probes for amyloid fibril formation are advantageous for the early detection and better understanding of this disease-associated process. Here, we report a comparative study of eight luminescent conjugated polythiophene derivates (LCPs) and their discrimination of a protein (insulin) in the native or amyloid-like fibrillar state. For two of the LCPs, the synthesis is reported. Compared to their monomer-based analogues, trimer-based LCPs showed significantly better optical signal specificity for amyloid-like fibrils, seen from increased quantum yield and spectral shift. The trimer-based LCPs alone were highly quenched and showed little interaction with native insulin, as seen from analytical ultracentrifugation and insignificant spectral differences from the trimer-based LCP in buffered and native protein solution. Hence, the trimer-based LCPs showed enhanced discrimination between the amyloid-like fibrillar state and the corresponding native protein.

  • 21.
    Åslund, Andreas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Synthesis of a pentathiophene fluorescent probe, 4’,3’’’-Bis-carboxymethyl-[2,2’;5’,2’’;5’’,2’’’;5’’’,2’’’‘]quinquethiophene-5,5’2010Inngår i: Nature Protocols, ISSN 1754-2189Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Poly and oligo-thiophenes have previously been used for in vitro, ex vivo and in vivo imaging of protein aggregates. The probe (p-FTAA) has been developed for the purpose of in vivo staining of protein aggregates such as amyloid deposits. It effectively passes the blood brain barrier and imaging can be performed live with two-photon imaging or ex vivo.

    The straightforward synthesis of p-FTAA, including two Suzuki couplings, makes it an attractive probe for studies of most diseases involving protein aggregates.

  • 22.
    Åslund, Andreas
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Sigurdson, Christina J
    Institute of Neuropathology, Department of Pathology, Universitätsspital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
    Klingstedt, Therése
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Kemi. Linköpings universitet, Tekniska fakulteten.
    Grathwohl, Stefan
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany.
    Bolmont, Tristan
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany.
    Dickstein, Dara L
    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
    Glimsdal, Eirik
    Department of Physics, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
    Prokop, Stefan
    Department of Neuropathology, Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany.
    Lindgren, Mikael
    Department of Physics, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
    Konradsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Holtzman, David M
    Department of Neurology, Alzheimer’s Disease Research Center, Washington University, St. Louis, Missouri 63110, USA.
    Hof, Patrick R
    Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029, USA.
    Heppner, Frank L
    Department of Neuropathology, Charité-Universitätsmedizin Berlin, D-13353 Berlin, Germany.
    Gandy, Samuel
    Alzheimer’s Disease Research Center, Mount Sinai School of Medicine, New York, New York 10029, USA.
    Jucker, Mathias
    Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tuebingen, D-72076 Tuebingen, Germany.
    Aguzzi, Adriano
    Institute of Neuropathology, Department of Pathology, Universitätsspital Zürich, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
    Hammarström, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biokemi. Linköpings universitet, Tekniska högskolan.
    Nilsson, Peter
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Organisk Kemi. Linköpings universitet, Tekniska högskolan.
    Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses2009Inngår i: ACS CHEMICAL BIOLOGY, ISSN 1554-8929, Vol. 4, nr 8, s. 673-684Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Molecular probes for selective Identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two, mouse-adapted prion strains. p-FTAA also revealed a transient soluble pre-fibrillar non-thioflavinophilic A beta-assemblies during in vitro fibrillation of A beta peptides. In brain tissue samples, A beta deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localliation with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual A beta plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimers disease, namely, A beta aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, A beta-tau interactions, and pathogenesis both ex vivo and in vivo.

1 - 22 of 22
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf