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Bäck, Marcus
Publications (10 of 17) Show all publications
Björk, L., Bäck, M., Lantz, L., Ghetti, B., Vidal, R., Klingstedt, T. & Nilsson, P. (2022). Proteophenes - Amino Acid Functionalized Thiophene-based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimers Disease Pathology. Chemistry - A European Journal, 28(62), Article ID e202201557.
Open this publication in new window or tab >>Proteophenes - Amino Acid Functionalized Thiophene-based Fluorescent Ligands for Visualization of Protein Deposits in Tissue Sections with Alzheimers Disease Pathology
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2022 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 28, no 62, article id e202201557Article in journal (Refereed) Published
Abstract [en]

Protein deposits composed of specific proteins or peptides are associated with several neurodegenerative diseases and fluorescent ligands able to detect these pathological hallmarks are vital. Here, we report the synthesis of a class of thiophene-based ligands, denoted proteophenes, with different amino acid side-chain functionalities along the conjugated backbone, which display selectivity towards specific disease-associated protein aggregates in tissue sections with Alzheimers disease (AD) pathology. The selectivity of the ligands towards AD associated pathological hallmarks, such as aggregates of the amyloid-beta (A beta) peptide or tau filamentous inclusions, was highly dependent on the chemical nature of the amino acid functionality, as well as on the location of the functionality along the pentameric thiophene backbone. Finally, the concept of synthesizing donor-acceptor-donor proteophenes with distinct photophysical properties was shown. Our findings provide the structural and functional basis for the development of new thiophene-based ligands that can be utilized for optical assignment of different aggregated proteinaceous species in tissue sections.

Place, publisher, year, edition, pages
Wiley-V C H Verlag GMBH, 2022
Keywords
Alzheimers disease; amyloid-beta; fluorescent ligands; protein aggregates; tau
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-188416 (URN)10.1002/chem.202201557 (DOI)000849809800001 ()35950816 (PubMedID)
Note

Funding Agencies|Swedish Research Council [201600748]; Swedish Brain Foundation; Swedish Alzheimer Foundation; Torsten Soderberg Foundation; U.S. National Institutes of Health [U01NS110437]

Available from: 2022-09-14 Created: 2022-09-14 Last updated: 2023-03-21Bibliographically approved
Rouhbakhsh, Z., Aili, D., Martinsson, E., Svärd, A., Bäck, M., Housaindokht, M. R., . . . Selegård, R. (2018). Self-Assembly of a Structurally Defined Chiro-Optical Peptide-Oligothiophene Hybrid Material. ACS Omega, 3(11), 15066-15075
Open this publication in new window or tab >>Self-Assembly of a Structurally Defined Chiro-Optical Peptide-Oligothiophene Hybrid Material
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2018 (English)In: ACS Omega, E-ISSN 2470-1343, Vol. 3, no 11, p. 15066-15075Article in journal (Refereed) Published
Abstract [en]

Conducting polymers are routinely used in optoelectronic biomaterials, but large polymer polydispersity and poor aqueous compatibility complicate integration with biomolecular templates and development of discrete and defined supramolecular complexes. Herein, we report on a chiro-optical hybrid material generated by the self-assembly of an anionic peptide and a chemically defined cationic pentameric thiophene in aqueous environment. The peptide acts as a stereochemical template for the thiophene and adopts an a-helical conformation upon association, inducing optical activity in the thiophene r-n * transition region. Theoretical calculations confirm the experimentally observed induced structural changes and indicate the importance of electrostatic interactions in the complex. The association process is also probed at the substrate-solvent interface using peptide-functionalized gold nanoparticles, indicating that the peptide can also act as a scaffold when immobilized, resulting in structurally well-defined supramolecular complexes. The hybrid complex could rapidly be assembled, and the kinetics of the formation could be monitored by utilizing the local surface plasmon resonance originating from the gold nanoparticles. We foresee that these findings will aid in designing novel hybrid materials and provide a possible route for the development of functional optoelectronic interfaces for both biomaterials and energy harvesting applications.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC, 2018
National Category
Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-153701 (URN)10.1021/acsomega.8b02153 (DOI)000451992500053 ()
Note

Funding Agencies|Knut and Alice Wallenberg Foundation; Swedish Foundation for Strategic Research; Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linkoping University [2009 00971]

Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2021-08-05
Snipstad, S., Hak, S., Baghirov, H., Sulheim, E., Mørch, Ý., Lélu, S., . . . Åslund, A. K. O. (2017). Labeling nanoparticles: Dye leakage and altered cellular uptake. Cytometry Part A, 91(8), 760-766
Open this publication in new window or tab >>Labeling nanoparticles: Dye leakage and altered cellular uptake
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2017 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 91, no 8, p. 760-766Article in journal (Refereed) Published
Abstract [en]

In vitro and in vivo behavior of nanoparticles (NPs) is often studied by tracing the NPs with fluorescent dyes. This requires stable incorporation of dyes within the NPs, as dye leakage may give a wrong interpretation of NP biodistribution, cellular uptake, and intracellular distribution. Furthermore, NP labeling with trace amounts of dye should not alter NP properties such as interactions with cells or tissues. To allow for versatile NP studies with a variety of fluorescence-based assays, labeling of NPs with different dyes is desirable. Hence, when new dyes are introduced, simple and fast screening methods to assess labeling stability and NP-cell interactions are needed. For this purpose, we have used a previously described generic flow cytometry assay; incubation of cells with NPs at 4 and 37C. Cell-NP interaction is confirmed by cellular fluorescence after 37C incubation, and NP-dye retention is confirmed when no cellular fluorescence is detected at 4C. Three different NP-platforms labeled with six different dyes were screened, and a great variability in dye retention was observed. Surprisingly, incorporation of trace amounts of certain dyes was found to reduce or even inhibit NP uptake. This work highlights the importance of thoroughly evaluating every dye-NP combination before pursuing NP-based applications. © 2016 International Society for Advancement of Cytometry.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
cellular uptake; flow cytometry; leakage; liposomes; nanoemulsions; polymeric nanoparticles
National Category
Cell Biology
Identifiers
urn:nbn:se:liu:diva-146318 (URN)10.1002/cyto.a.22853 (DOI)000408333700004 ()27077940 (PubMedID)2-s2.0-84963800614 (Scopus ID)
Available from: 2018-04-07 Created: 2018-04-07 Last updated: 2018-04-19Bibliographically approved
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, 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: 2024-07-04Bibliographically 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, E-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: 2021-01-26Bibliographically approved
Magnusson, K., Appelqvist, H., Cieślar-Pobuda, A., Bäck, M., Kågedal, B., Jonasson, J., . . . Nilsson, P. R. (2015). An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells. Frontiers in Chemistry, 3, Article ID 58.
Open this publication in new window or tab >>An imidazole functionalized pentameric thiophene displays different staining patterns in normal and malignant cells
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2015 (English)In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 3, article id 58Article in journal (Refereed) Published
Abstract [en]

Molecular tools for fluorescent imaging of cells and their components are vital for understanding the function and activity of cells. Here, we report an imidazole functionalized pentameric oligothiophene, p-HTIm, that can be utilized for fluorescent imaging of cells. p-HTIm fluorescence in normal cells appeared in a peripheral punctate pattern partially co-localized with lysosomes, whereas a one-sided perinuclear Golgi associated localization of the dye was observed in malignant cells. The uptake of p-HTIm was temperature dependent and the intracellular target was reached within 1 h after staining. The ability of p-HTIm to stain cells was reduced when the imidazole side chain was chemically altered, verifying that specific imidazole side-chain functionalities are necessary for achieving the observed cellular staining. Our findings confirm that properly functionalized oligothiophenes can be utilized as fluorescent tools for vital staining of cells and that the selectivity towards distinct intracellular targets are highly dependent on the side-chain functionalities along the conjugated thiophene backbone.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2015
Keywords
Oligothiophenes, fluorescence, cells, imaging, imidazole
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology
Identifiers
urn:nbn:se:liu:diva-121813 (URN)10.3389/fchem.2015.00058 (DOI)000373364600001 ()
Note

Vid tiden för disputation förelåg publikationen som manuskript

Funding agencies:  Swedish Foundation for Strategic Research; GeCONil [POIG.02.03.01-24-099/13]; ERC from the European Research Council

Available from: 2015-10-07 Created: 2015-10-07 Last updated: 2017-12-01Bibliographically approved
Cieslar-Pobuda, A., Bäck, M., Magnusson, K., Vilas Jain, M., Rafat, M., Ghavami, S., . . . Los, M. J. (2014). Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives. Cytometry Part A, 85A(7), 628-635
Open this publication in new window or tab >>Cell Type Related Differences in Staining with Pentameric Thiophene Derivatives
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2014 (English)In: Cytometry Part A, ISSN 1552-4922, E-ISSN 1552-4930, Vol. 85A, no 7, p. 628-635Article in journal (Refereed) Published
Abstract [en]

Fluorescent compounds capable of staining cells selectively without affecting their viability are gaining importance in biology and medicine. Recently, a new family of optical dyes, denoted luminescent conjugated oligothiophenes (LCOs), has emerged as an interesting class of highly emissive molecules for studying various biological phenomena. Properly functionalized LCOs have been utilized for selective identification of disease-associated protein aggregates and for selective detection of distinct cells. Herein, we present data on differential staining of various cell types, including cancer cells. The differential staining observed with newly developed pentameric LCOs is attributed to distinct side chain functionalities along the thiophene backbone. Employing flow cytometry and fluorescence microscopy we examined a library of LCOs for stainability of a variety of cell lines. Among tested dyes we found promising candidates that showed strong or moderate capability to stain cells to different extent, depending on target cells. Hence, LCOs with diverse imidazole motifs along the thiophene backbone were identified as an interesting class of agents for staining of cancer cells, whereas LCOs with other amino acid side chains along the backbone showed a complete lack of staining for the cells included in the study. Furthermore, for p-HTMI,a LCO functionalized with methylated imidazole moieties, the staining was dependent on the p53 status of the cells, indicating that the molecular target for the dye is a cellular component regulated by p53. We foresee that functionalized LCOs will serve as a new class of optical ligands for fluorescent classification of cells and expand the toolbox of reagents for fluorescent live imaging of different cells.

Place, publisher, year, edition, pages
John Wiley & Sons, 2014
Keywords
cancer stem cells; luminescent conjugated oligothiophenes; fluorescent probes
National Category
Clinical Medicine Chemical Sciences Medical Biotechnology Computer and Information Sciences
Identifiers
urn:nbn:se:liu:diva-109171 (URN)10.1002/cyto.a.22437 (DOI)000338007700010 ()24500794 (PubMedID)
Available from: 2014-08-12 Created: 2014-08-11 Last updated: 2018-01-11Bibliographically approved
Simon, R., Shirani, H., Åslund, K. O., Bäck, M., Haroutunian, V., Gandy, S. & Nilsson, P. R. (2014). Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts. Chemistry - A European Journal, 20(39), 12537-12543
Open this publication in new window or tab >>Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts
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2014 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 39, p. 12537-12543Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2014
Keywords
fluorescence; imaging agents; luminescent conjugated oligothiophenes; protein aggregates; solvatochromism
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-111655 (URN)10.1002/chem.201402890 (DOI)000342626200026 ()25111601 (PubMedID)
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2024-01-10Bibliographically approved
Simon, R., Bäck, M., Shirani, H., Lindgren, M. & Nilsson, P. R. (2014). pH-dependent optical transitions in anionic pentameric oligothiophenes.
Open this publication in new window or tab >>pH-dependent optical transitions in anionic pentameric oligothiophenes
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Understanding the photo-physical processes in fluorescent probes are essential as such dyes are widely utilized in molecular biology. Here we report the pH-dependent optical transitions of a library of anionic pentameric luminescent conjugated oligothiophenes (LCOs) that have been used for fluorescent identification of protein aggregates, the pathological hallmark of many devastating diseases. Absorption-, excitation- and emission spectra were recorded for all LCOs in different buffers with a pH range from 3.5 to 7. p-FTAA, a LCO having a central core consisting of a trimeric thiophene  building block with head-to-head acetic acid functionalization as well as terminal carboxyl groups extending the pentameric thiophene backbone, displayed pH/dependent optical characteristics correlating to a non-planar to planar transition of the conjugated backbone as well as aggregation between adjacent thiophene chain upon protonation of the  acetic acid side chains. In contrast, chemically related analogues to p-FTAA lacking the  terminal carboxyl groups extending the pentameric thiophene backbone or the conformational ability to undergo a non/planar to planar transition of the  conjugated backbone, displayed different optical characteristics compared to p-FTAA. Overall these studies highlighted that minor chemical alteration of LCOs can result in major difference in the optical characteristics obtained from the dyes and the results might aid in designing novel LCOs that have  superior optical performance as amyloid ligands.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-111656 (URN)
Available from: 2014-10-28 Created: 2014-10-28 Last updated: 2014-10-28Bibliographically approved
Sandgren, V., Bäck, M., Kvarnström, I. & Dahlgren, A. (2013). Design and synthesis of hydroxyethylene-based BACE-1 inhibitors incorporating extended P1 substituents. Open Medicinal Chemistry Journal, 7, 1-15
Open this publication in new window or tab >>Design and synthesis of hydroxyethylene-based BACE-1 inhibitors incorporating extended P1 substituents
2013 (English)In: Open Medicinal Chemistry Journal, ISSN 1874-1045, Vol. 7, p. 1-15Article in journal (Refereed) Published
Abstract [en]

Novel BACE-1 inhibitors with a hydroxyethylene central core have been  developed. Modified P1´ and extended P1 substituents were incorporated with the aim to explore potential interactions with the S1´ and the S1-S3 pocket, respectively, of BACE-1. Inhibitors were identified displaying IC50 values in the nanomolar range, i.e., 69 nM for the most potent compound. Possible inhibitor interactions with the enzyme are also discussed.

Place, publisher, year, edition, pages
Bussum, Netherlands: Bentham Open, 2013
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-76171 (URN)10.2174/1874104501307010001 (DOI)
Available from: 2012-03-29 Created: 2012-03-29 Last updated: 2017-12-07Bibliographically approved
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