liu.seSearch for publications in DiVA
Change search
Link to record
Permanent link

Direct link
BETA
Alternative names
Publications (10 of 117) Show all publications
Elgland, M., Nordeman, P., Fyrner, T., Antoni, G., Nilsson, P. & Konradsson, P. (2017). beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET. New Journal of Chemistry, 41(18), 10231-10236
Open this publication in new window or tab >>beta-Configured clickable [F-18] FDGs as novel F-18-fluoroglycosylation tools for PET
Show others...
2017 (English)In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 41, no 18, p. 10231-10236Article in journal (Refereed) Published
Abstract [en]

In oncology and neurology the F-18-radiolabeled glucose analogue 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]FDG) is by far the most commonly employed metabolic imaging agent for positron emission tomography (PET). Herein, we report a novel synthetic route to beta-configured mannopyranoside precursors and a chemoselective F-18-fluoroglycosylation method that employ two b-configured [F-18]FDG derivatives equipped with either a terminal azide or alkyne aglycon respectively, for use as a CuAAC clickable tool set for PET. The b-configured precursors provided the corresponding [F-18]FDGs in a radiochemical yield of 77-88%. Further, the clickability of these [F-18]FDGs was investigated by click coupling to the suitably functionalized Fmoc-protected amino acids, Fmoc-N-(propargyl)-glycine and Fmoc-3-azido-L-alanine, which provided the F-18-fluoroglycosylated amino acid conjugates in radiochemical yields of 75-83%. The F-18-fluoroglycosylated amino acids presented herein constitute a new and interesting class of metabolic PET radiotracers.

Place, publisher, year, edition, pages
ROYAL SOC CHEMISTRY, 2017
National Category
Organic Chemistry
Identifiers
urn:nbn:se:liu:diva-141934 (URN)10.1039/c7nj00716g (DOI)000411767400073 ()
Note

Funding Agencies|Swedish Foundation for Strategic Research; Swedish Research Council

Available from: 2017-10-13 Created: 2017-10-13 Last updated: 2018-02-21
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
Show others...
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
Nyström, S., Vahdat Shariat Panahi, A., Nilsson, P., Westermark, P., Westermark, G. T., Hammarström, P. & Lundmark, K. (2017). Seed-dependent templating of murine AA amyloidosis. Amyloid: Journal of Protein Folding Disorders, 24(sup1), 140-141
Open this publication in new window or tab >>Seed-dependent templating of murine AA amyloidosis
Show others...
2017 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 24, no sup1, p. 140-141Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

n/a

Place, publisher, year, edition, pages
Taylor & Francis, 2017
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-145569 (URN)10.1080/13506129.2017.1290599 (DOI)000399943700076 ()28434369 (PubMedID)2-s2.0-85018736877 (Scopus ID)
Available from: 2018-03-25 Created: 2018-03-25 Last updated: 2018-05-03Bibliographically 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
Show others...
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
Novotny, R., Langer, F., Mahler, J., Skodras, A., Vlachos, A., Wegenast-Braun, B. M., . . . Jucker, M. (2016). Conversion of Synthetic A beta to In Vivo Active Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model. Journal of Neuroscience, 36(18), 5084-5093
Open this publication in new window or tab >>Conversion of Synthetic A beta to In Vivo Active Seeds and Amyloid Plaque Formation in a Hippocampal Slice Culture Model
Show others...
2016 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 36, no 18, p. 5084-5093Article in journal (Refereed) Published
Abstract [en]

The aggregation of amyloid-beta peptide (A beta) inbrain is an early event and hallmark of Alzheimers disease (AD). We combined the advantages of in vitro and in vivo approaches to study cerebral beta-amyloidosis by establishing a long-term hippocampal slice culture(HSC) model. While no A beta deposition was noted in untreated HSCs of postnatal A beta precursor protein transgenic (APP tg) mice, A beta deposition emerged in HSCs when cultures were treated once with brain extract from aged APP tg mice and the culture medium was continuously supplemented with synthetic A beta. Seeded A beta deposition was also observed under the same conditions in HSCs derived from wild-type or App-null mice but in no comparable way when HSCs were fixed before cultivation. Both the nature of the brain extract and the synthetic A beta species determined the conformational characteristics of HSCA beta deposition. HSCA beta deposits induced a microglia response, spine loss, and neuritic dystrophy but no obvious neuron loss. Remarkably, in contrast to in vitro aggregated synthetic A beta, homogenates of A beta deposits containing HSCs induced cerebral beta-amyloidosis upon intracerebral inoculation into young APP tg mice. Our results demonstrate that a living cellular environment promotes the seeded conversion of synthetic A beta into a potent in vivo seeding-active form.

Place, publisher, year, edition, pages
SOC NEUROSCIENCE, 2016
Keywords
alzheimer; amyloid; neurodegeneration; prion-like seeding; slice culture
National Category
Neurosciences
Identifiers
urn:nbn:se:liu:diva-130301 (URN)10.1523/JNEUROSCI.0258-16.2016 (DOI)000378276600016 ()27147660 (PubMedID)
Note

Funding Agencies|German Federal Ministry of Education and Research Grant [BMBF-ALZKULT 031A198]; EU Joint Programme on Neurodegenerative Diseases Grant JPND-NeuTARGETs; German Research Foundation [DFG DE 551/11-2, VL 72/1-2]

Available from: 2016-07-31 Created: 2016-07-28 Last updated: 2018-01-10
Sjölander, D., Roecken, C., Westermark, P., Westermark, G. T., Nilsson, P. & Hammarström, P. (2016). Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid. Amyloid: Journal of Protein Folding Disorders, 23(2), 98-108
Open this publication in new window or tab >>Establishing the fluorescent amyloid ligand h-FTAA for studying human tissues with systemic and localized amyloid
Show others...
2016 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 23, no 2, p. 98-108Article in journal (Refereed) Published
Abstract [en]

Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. The only functional structure stained with h-FTAA showing the amyloidotypic fluorescence spectrum was Paneth cell granules in intestine. Screening of 114 amyloid containing tissues derived from 107 verified (Congo red birefringence and/or immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence (107/107, 100% sensitivity). The majority of Congo red negative control cases (27 of 32, 85% specificity) were negative with h-FTAA. Small Congo red negative aggregates in kidney, liver, pancreas and duodenum were found by h-FTAA fluorescence in five control patients aged 72-83 years suffering from diverse diseases. The clinical significance of these false-positive lesions is currently not known. Because h-FTAA fluorescence is one magnitude brighter than Congo red and as the staining is performed four magnitudes lower than the concentration of dye, we believe that these inclusions are beyond detection by Congo red. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. Use of h-FTAA can be exploited as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. Our results also implicate the potential of the technique for detection of prodromal amyloidosis as well as for discovery of new amyloid-like protein aggregates in humans.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2016
Keywords
Amyloidosis; Congo red; diagnosis; fluorescence; microscopy; oligothiophenes; screening
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-128924 (URN)10.3109/13506129.2016.1158159 (DOI)000375905000004 ()26987044 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Swedish Research Council; Goran Gustafsson Foundation; Linkoping University Center of Neuroscience; European Research Council (ERC starting grant; Project MUMID); EU-FP7 Health programme project LUPAS; Selanders Foundation; patients association FAM; patients association FAMY Norrbotten; patients association Amyl

Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2018-04-25
Bednarska, N. G., van Eldere, J., Gallardo, R., Ganesan, A., Ramakers, M., Vogel, I., . . . Rousseau, F. (2016). Protein aggregation as an antibiotic design strategy. Molecular Microbiology, 99(5), 849-865
Open this publication in new window or tab >>Protein aggregation as an antibiotic design strategy
Show others...
2016 (English)In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 99, no 5, p. 849-865Article in journal (Refereed) Published
Abstract [en]

Taking advantage of the xenobiotic nature of bacterial infections, we tested whether the cytotoxicity of protein aggregation can be targeted to bacterial pathogens without affecting their mammalian hosts. In particular, we examined if peptides encoding aggregation-prone sequence segments of bacterial proteins can display antimicrobial activity by initiating toxic protein aggregation in bacteria, but not in mammalian cells. Unbiased in vitro screening of aggregating peptide sequences from bacterial genomes lead to the identification of several peptides that are strongly bactericidal against methicillin-resistant Staphylococcus aureus. Upon parenteral administration in vivo, the peptides cured mice from bacterial sepsis without apparent toxic side effects as judged from histological and hematological evaluation. We found that the peptides enter and accumulate in the bacterial cytosol where they cause aggregation of bacterial polypeptides. Although the precise chain of events that leads to cell death remains to be elucidated, the ability to tap into aggregation-prone sequences of bacterial proteomes to elicit antimicrobial activity represents a rich and unexplored chemical space to be mined in search of novel therapeutic strategies to fight infectious diseases.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-127057 (URN)10.1111/mmi.13269 (DOI)000371241600005 ()26559925 (PubMedID)
Note

Funding Agencies|VIB; University of Leuven; Funds for Scientific Research Flanders (FWO); Flanders Institute for Science and Technology (IWT); Federal Office for Scientific Affairs of Belgium (Belspo) [IUAP P7/16]; Swedish Foundation for Strategic Research; Swedish Research Council; ERC Starting Independent Researcher Grant (Project: MUMID) from the European Research Council

Available from: 2016-04-13 Created: 2016-04-13 Last updated: 2018-09-14
Gabrielsson, E., Armgarth, A., Hammarström, P., Nilsson, P. & Berggren, M. (2016). Spatiotemporal Control of Amyloid-Like A Plaque Formation Using a Multichannel Organic Electronic Device. Macromolecular materials and engineering (Print), 301(4), 359-363
Open this publication in new window or tab >>Spatiotemporal Control of Amyloid-Like A Plaque Formation Using a Multichannel Organic Electronic Device
Show others...
2016 (English)In: Macromolecular materials and engineering (Print), ISSN 1438-7492, E-ISSN 1439-2054, Vol. 301, no 4, p. 359-363Article in journal (Refereed) Published
Abstract [en]

We herein report on an iontronic device to drive and control A1-40 and A1-42 fibril formation. This system allows kinetic control of A aggregation by regulation of H+ flows. The formed aggregates show both nanometer-sized fibril structure and microscopic growth, thus mimicking senile plaques, at the H+-outlet. Mechanistically we observed initial accumulation of A1-40 likely driven by electrophoretic migration which preceded nucleation of amyloid structures in the accumulated peptide cluster.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2016
Keywords
amyloid; Alzheimers disease; bioelectronics; fibrils; luminescent conjugated oligothiophene; optical probes
National Category
Electrical Engineering, Electronic Engineering, Information Engineering Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-127750 (URN)10.1002/mame.201500428 (DOI)000374030400001 ()
Note

Funding Agencies|VINNOVA [2010-00507]; Swedish research council [2011-5804, 621-2011-3517]; Advanced Functional Materials Center at Linkoping University; Onnesjo foundation; ERC Starting Independent Researcher Grant (Project: MUMID) from the European Research Council

Available from: 2016-05-12 Created: 2016-05-12 Last updated: 2018-04-25
Shirani, H., Linares, M., Sigurdson, C. J., Lindgren, M., Norman, P. & Nilsson, P. (2015). A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates. Chemistry - A European Journal, 21(43), 15133-15137
Open this publication in new window or tab >>A Palette of Fluorescent Thiophene-Based Ligands for the Identification of Protein Aggregates
Show others...
2015 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 21, no 43, p. 15133-15137Article in journal (Refereed) Published
Abstract [en]

By replacing the central thiophene unit of an anionic pentameric oligothiophene with other heterocyclic moities, a palette of pentameric thiophene-based ligands with distinct fluorescent properties were synthesized. All ligands displayed superior selectivity towards recombinant amyloid fibrils as well as disease-associated protein aggregates in tissue sections.

Place, publisher, year, edition, pages
WILEY-V C H VERLAG GMBH, 2015
Keywords
Alzheimers disease; fluorescent probes; luminescence; oligothiophenes; microscopy
National Category
Chemical Sciences
Identifiers
urn:nbn:se:liu:diva-122776 (URN)10.1002/chem.201502999 (DOI)000363332200011 ()26388448 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research; Erling Persson foundation; Alzheimers Disease Research Center (NIH) [AGO 5131]; ERC from the European Research Council; Swedish e-Science Research Center (SeRC); Swedish Research Council [621-2014-4646]

Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2017-12-01
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
Show others...
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: 2017-12-05
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5582-140X

Search in DiVA

Show all publications