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Johansson, Leif B. G.
Alternative names
Publications (8 of 8) Show all publications
Nordeman, P., Johansson, L. B. G., Bäck, M., Estrada, S., Hall, H., Sjölander, D., . . . Antoni, G. (2016). 11C and 18FRadiolabeling of Tetra- and Pentathiophenes as PET-ligands for Amyloid Protein Aggregates. ACS Medicinal Chemistry Letters, 7(4), 368-373
Open this publication in new window or tab >>11C and 18FRadiolabeling of Tetra- and Pentathiophenes as PET-ligands for Amyloid Protein Aggregates
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2016 (English)In: ACS Medicinal Chemistry Letters, ISSN 1948-5875, E-ISSN 1948-5875, Vol. 7, no 4, p. 368-373Article in journal (Refereed) Published
Abstract [en]

Three oligothiophenes were evaluated as PET tracers for the study of local and systemic amyloidosis ex vivo using tissue from patients with amyloid deposits and in vivo using healthy animals and PET-CT. The ex vivo binding studies revealed that all three labeled compounds bound specifically to human amyloid deposits. Specific binding was found in the heart, kidney, liver and spleen. To verify the specificity of the oligothiophenes towards amyloid deposits, tissue sections with amyloid pathology were stained using the fluorescence exhibited by the compounds and evaluated with multiphoton microscopy. Furthermore, in vivo rat and monkey PET-CT studies showed very low uptake in the brain, pancreas and heart of the healthy animals indicating low non-specific binding to healthy tissue. The biological evaluations indicated that this is a promising group of compounds for the visualization of systemic and localized amyloidosis.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Chemical Sciences Cell Biology
Identifiers
urn:nbn:se:liu:diva-122273 (URN)10.1021/acsmedchemlett.5b00309 (DOI)000374436700007 ()
Note

Funding agencies:  Swedish Research Council; Swedish Foundation for Strategic Research; LiU-Neuro; Ehrling-Persson Foundation; Goran-Gustafsson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)

Vid tiden för disputation förelåg publikationen som manuskript

Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2018-04-25Bibliographically approved
Choong, F., Bäck, M., Fahlen, S., Johansson, L. B. G., Melican, K., Rhen, M., . . . Richter-Dahlfors, A. (2016). Real-time opto-tracing of curli and cellulose in live Salmonella biofilms using conjugated oligothiophenes. npj Biofilms and Microbiomes, 2, Article ID 16024.
Open this publication in new window or tab >>Real-time opto-tracing of curli and cellulose in live Salmonella biofilms using conjugated oligothiophenes
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2016 (English)In: npj Biofilms and Microbiomes, ISSN 2055-5008, Vol. 2, article id 16024Article in journal (Refereed) Published
Abstract [en]

Extracellular matrix (ECM) is the protein- and polysaccharide-rich backbone of bacterial biofilms that provides a defensive barrier in clinical, environmental and industrial settings. Understanding the dynamics of biofilm formation in native environments has been hindered by a lack of research tools. Here we report a method for simultaneous, real-time, in situ detection and differentiation of the Salmonella ECM components curli and cellulose, using non-toxic, luminescent conjugated oligothiophenes (LCOs). These flexible conjugated polymers emit a conformation-dependent fluorescence spectrum, which we use to kinetically define extracellular appearance of curli fibres and cellulose polysaccharides during bacterial growth. The scope of this technique is demonstrated by defining biofilm morphotypes of Salmonella enterica serovars Enteritidis and Typhimurium, and their isogenic mutants in liquid culture and on solid media, and by visualising the ECM components in native biofilms. Our reported use of LCOs across a number of platforms, including intracellular cellulose production in eukaryotic cells and in infected tissues, demonstrates the versatility of this optotracing technology, and its ability to redefine biofilm research.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-160729 (URN)10.1038/npjbiofilms.2016.24 (DOI)000419466300019 ()28721253 (PubMedID)2-s2.0-85020828677 (Scopus ID)
Available from: 2019-10-04 Created: 2019-10-04 Last updated: 2019-12-03Bibliographically approved
Johansson, L. B. G., Simon, R., Bergström, G., Eriksson, M., Prokop, S., Mandenius, C.-F., . . . Nilsson, P. (2015). An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates. Biosensors & bioelectronics, 63, 204-211
Open this publication in new window or tab >>An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates
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2015 (English)In: Biosensors & bioelectronics, ISSN 0956-5663, E-ISSN 1873-4235, Vol. 63, p. 204-211Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Protein aggregates; Oligothiophene; Fluorescence; Surface plasmon resonance; Click chemistry
National Category
Chemical Sciences Biological Sciences
Identifiers
urn:nbn:se:liu:diva-112169 (URN)10.1016/j.bios.2014.07.042 (DOI)000343337000030 ()25089818 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Ehrling Persson Foundation; ERC Starting Independent Researcher grant (Project: MUMID)

Available from: 2014-11-18 Created: 2014-11-18 Last updated: 2019-01-22
Johansson, L. B. .. (2015). Asymmetric Oligothiophenes: Chemical Evolution of Multimodal Amyloid Ligands. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Asymmetric Oligothiophenes: Chemical Evolution of Multimodal Amyloid Ligands
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Luminescent conjugated polymers (LCPs) and luminescent conjugated oligothiophenes (LCOs) can be used as molecular probes to study diseases associated with protein aggregation. The conventionally used dyes to study and detect protein aggregates, denoted amyloid, have been Congo red (CR) and Thioflavin T (ThT). In contrast to these amyloid ligands, LCOs offer the possibility to detect aggregated proteinaceous species occurring at earlier stages of amyloid formation as well as to distinguish different morphotypes of protein aggregates. The interaction between the LCOs and the protein deposits can be studied by fluorescence spectroscopy and microscopy both in vitro and ex vivo. In this thesis we report the development of multimodal asymmetric LCOs that can be utilized with two novel techniques, Surface Plasmon Resonance (SPR) and Positron Emission Tomography (PET), to study the interaction between LCO and amyloid fibrils in real time. With SPR, we have been able to determine binding affinities between LCO and amyloid, and with PET we have shown that radiolabelled LCOs can be used as a non-invasive method to study amyloid deposits in vivo. In addition, by alteration of the backbone (change of thiophene units), and of adding different side chains functionalities, we have shown that the properties of the amyloid ligands have a huge impact of the binding to different stages or forms of protein aggregates. By making asymmetrical LCOs, which can be attached to a surface, we also foresee a methodology that will offer the possibility to create a sensitive and selective detection method, and maybe lead to a lab-on-a-chip-application.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2015. p. 67
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1692
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-122278 (URN)10.3384/diss.diva-122278 (DOI)978-91-7685-987-2 (ISBN)
Public defence
2015-11-20, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (Swedish)
Opponent
Supervisors
Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2019-11-15Bibliographically approved
Nyström, S., Psonka-Antonczyk, K. M., Ellingsen, P. G., Johansson, L., Reitan, N., Handrick, S., . . . Nilsson, P. K. (2013). Evidence for Age-Dependent in Vivo Conformational Rearrangement within A beta Amyloid Deposits. ACS Chemical Biology, 8(6), 1128-1133
Open this publication in new window or tab >>Evidence for Age-Dependent in Vivo Conformational Rearrangement within A beta Amyloid Deposits
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2013 (English)In: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 8, no 6, p. 1128-1133Article in journal (Refereed) Published
Abstract [en]

Deposition of aggregated A beta peptide in the brain is one of the major hallmarks of Alzheimers disease. Using a combination of two structurally different, but related, hypersensitive fluorescent amyloid markers, LCOs, reporting on separate ultrastructural elements, we show that conformational rearrangement occurs within A beta plaques of transgenic mouse models as the animals age. This important mechanistic insight should aid the design and evaluation of experiments currently using plaque load as readout.

Place, publisher, year, edition, pages
American Chemical Society, 2013
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-96432 (URN)10.1021/cb4000376 (DOI)000320979300006 ()
Note

Funding Agencies|EU-FP7 Health Programme Project LUPAS||Swedish Alzheimer Foundation||Swedish Research Council||Knut and Alice Wallenberg Foundation||Swedish Foundation for Strategic Research||European Research Council (ERC)||Norwegian Research Council|183338/S10|Georg and Astrid Olsson||

Available from: 2013-09-17 Created: 2013-08-19 Last updated: 2019-11-08
Nystrom, S., Nelson, E., Reitan, N., Ellingsen, P., Brorsson, A.-C., Mason, J., . . . Hammarström, P. (2012). Monitoring amyloid formation and maturation in vitro and in vivo using LCO fluorescence in PRION, vol 6, issue , pp 13-13. In: PRION: . Paper presented at Prion2012 (pp. 13-13). Landes Bioscience, 6
Open this publication in new window or tab >>Monitoring amyloid formation and maturation in vitro and in vivo using LCO fluorescence in PRION, vol 6, issue , pp 13-13
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2012 (English)In: PRION, Landes Bioscience , 2012, Vol. 6, p. 13-13Conference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Landes Bioscience, 2012
National Category
Engineering and Technology
Identifiers
urn:nbn:se:liu:diva-78587 (URN)000304234300027 ()
Conference
Prion2012
Available from: 2012-06-15 Created: 2012-06-15 Last updated: 2018-04-25
Klingstedt, T., Åslund, A., Simon, R., Johansson, L. B. G., Mason, J., Nyström, S., . . . Nilsson, P. (2011). Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates. Organic and biomolecular chemistry, 9(24), 8356-8370
Open this publication in new window or tab >>Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates
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2011 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, no 24, p. 8356-8370Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2011
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-73487 (URN)10.1039/c1ob05637a (DOI)000297354100019 ()
Available from: 2012-01-04 Created: 2012-01-04 Last updated: 2019-11-08
Johansson, L. B. G., Bäck, M., Lantz, L., Eriksson, M., Nygren, P. & Nilsson, P. R.A variety of thiophene based ligands for detection of protein aggregates by surface plasmon resonance.
Open this publication in new window or tab >>A variety of thiophene based ligands for detection of protein aggregates by surface plasmon resonance
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

By attaching an azide functional group via a tetraethylene glycol linker to the α-terminal position of a variety of oligothiophenes, thiophene-based ligands that can be utilized for detection of protein aggregates with surface plasmon resonance have been developed. All ligands displayed selectivity towards recombinant amyloid fibrils and the LCO/protein aggregate interaction could be detected by fluorescence as well as by surface plasmon resonance.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-122274 (URN)
Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2015-10-27Bibliographically approved
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