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  • 301.
    Engler, Henry
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Nennesmo, Inger
    Kumlien, Eva
    Gambini, JP
    Lundberg, PO
    Savitcheva, Irina
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Imaging astrocytosis with PET in Creutzfeldt-Jakob disease: case report with histopathological findings2012In: International Journal of Clinical and Experimental Medicine, ISSN 1940-5901, E-ISSN 1940-5901, Vol. 5, no 2, p. 201-207Article in journal (Refereed)
    Abstract [en]

    In a previous study, patients with suspect Creutzfeldt-Jakob's disease (CJD) have been examined with Positron Emission Tomography (PET) combining N-[11C-methyl]-L-deuterodeprenyl (DED) and [(18)F] 2- fluorodeoxyglucose (FDG) in an attempt to detect astrocytosis and neuronal dysfunction, two of the hallmarks in CJD. Increased DED uptake with pronounced hypometabolism matching the areas with high DED retention was found in the fronto-parieto-occipital areas and cerebellum of patients with confirmed CJD. However, the temporal lobes did not present such a pattern. In 6 of the 15 examined patients the autopsy was performed, but a strict comparison between the PET results and the histopathology could not be done. Recently, one patient with suspect CJD was examined with PET using DED and FDG. The results of the examinations in this patient showed a pattern similar to that found in the brain of the CJD patients from the first study. The patient died shortly after the examination and an autopsy could be performed. The autopsy showed neuronal death, astrocytosis and spongiform changes in the brain. The diagnosis of definite sporadic CJD was established by the Western blot analysis, confirming the presence of the prion resistant protein (PrPres). The PET data demonstrated high DED uptake and extreme low glucose uptake in the left brain hemisphere whereas the right side was less affected. The autopsy was performed allowing the comparison between high DED uptake and the histopathological findings of reactive astrocytosis revealed by immunostaining with antibodies against glial fibrillary acid protein (GFAP). The results confirmed the presence of a pattern with high ratio DED/FDG, similar to that found in the previous study and revealing for the first time, a good correlation between high DED uptake and high density of reactive astrocytes as demonstrated by immunostaining.

  • 302.
    Englund, Elias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Pattanaik, Bagmi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Ubhayasekera, Sarojini J.K.A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Stensjö, Karin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Lindberg, Pia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Production of Squalene in Synechocystis sp. PCC 68032014In: PLoS ONE, Vol. 9, no 3, p. e90270-Article in journal (Refereed)
    Abstract [en]

    In recent years, there has been an increased interest in the research and development of sustainable alternatives to fossil fuels. Using photosynthetic microorganisms to produce such alternatives is advantageous, since they can achieve direct conversion of carbon dioxide from the atmosphere into the desired product, using sunlight as the energy source. Squalene is a naturally occurring 30-carbon isoprenoid, which has commercial use in cosmetics and in vaccines. If it could be produced sustainably on a large scale, it could also be used instead of petroleum as a raw material for fuels and as feedstock for the chemical industry. The unicellular cyanobacterium Synechocystis PCC 6803 possesses a gene, slr2089, predicted to encode squalene hopene cyclase (Shc), an enzyme converting squalene into hopene, the substrate for forming hopanoids. Through inactivation of slr2089 (shc), we explored the possibility to produce squalene using cyanobacteria. The inactivation led to accumulation of squalene, to a level over 70 times higher than in wild type cells, reaching 0.67 mg OD750−1 L−1. We did not observe any significant growth deficiency in the Δshc strain compared to the wild type Synechocystis, even at high light conditions, suggesting that the observed squalene accumulation was not detrimental to growth, and that formation of hopene by Shc is not crucial for growth under normal conditions, nor for high-light stress tolerance. Effects of different light intensities and growth stages on squalene accumulation in the Δshc strain were investigated. We also identified a gene, sll0513, as a putative squalene synthase in Synechocystis, and verified its function by inactivation. In this work, we show that it is possible to use the cyanobacterium Synechocystis to generate squalene, a hydrocarbon of commercial interest and a potential biofuel. We also report the first identification of a squalene hopene cyclase, and the second identification of squalene synthase, in cyanobacteria.

  • 303.
    Engman, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Åhs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Furmark, Tomas
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Linnman, Clas
    Pissiota, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Appel, Lieuwe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Frans, Örjan
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Fredrikson, Mats
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Age, sex and NK1 receptors in the human brain: A positron emission tomography study with [C-11]GR2051712012In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 22, no 8, p. 562-568Article in journal (Refereed)
    Abstract [en]

    The substance P/neurokinin 1 (SP/NK1) system has been implicated in the processing of negative affect. Its role seems complex and findings from animal studies have not been easily translated to humans. Brain imaging studies on NK1 receptor distribution in humans have revealed an abundance of receptors in cortical, striatal and subcortical areas, including the amygdala. A reduction in NK1 receptors with increasing age has been reported in frontal, temporal, and parietal cortices, as well as in hippocampal areas. Also, a previous study suggests sex differences in cortical and subcortical areas, with women displaying fewer NK1 receptors. The present PET study explored NK1 receptor availability in men (n = 9) and women (n = 9) matched for age varying between 20 and 50 years using the highly specific NK1 receptor antagonist [11C]GR205171 and a reference tissue model with cerebellum as the reference region. Age by sex interactions in the amygdala and the temporal cortex reflected a lower NK1 receptor availability with increasing age in men, but not in women. A general age-related decline in NK1 receptor availability was evident in the frontal, temporal, and occipital cortices, as well as in the brainstem, caudate nucleus, and thalamus. Women had lower NK1 receptor availability in the thalamus. The observed pattern of NK1 receptor distribution in the brain might have functional significance for brain-related disorders showing age- and sex-related differences in prevalence.

  • 304.
    Engman, Mattias
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Cheruku, Pradeep
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Kaukoranta, Päivi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Völker, Sebastian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Andersson, Pher
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry.
    Highly Selective Iridium-Catalyzed Asymmetric Hydrogenation of Trifluoromethyl Olefins: A New Route to Trifluoromethyl- Bearing Stereocenters2009In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 351, no 3, p. 375-378Article in journal (Refereed)
    Abstract [en]

    Fluorine-containing compounds are useful in many applications ranging from pharmaceuticals to ferroelectric crystals. We have developed a new, highly enantioselective synthetic route to trifluoromethyl-bearing stereocenters in up to 96% ee via asymmetric hydrogenation using N,P-ligated iridium catalysts. We also hydrogenated an isomeric mixture of olefins; this reaction gave the hydrogenation product highly enantioselectively (87% ee), and only the E isomer was present after the reaction had reached 56% conversion.

  • 305.
    Engström, Lorentz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Zetterqvist, Örjan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Ragnarsson, Ulf
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Ek, Pia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Dahlqvist-Edberg, Ulla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The cyclic AMP-dependent phosphorylation of pyruvate kinase as a model in the study of regulation and turnover of phosphorylated proteins1982In: Progress in clinical and biological research, ISSN 0361-7742, Vol. 102, no Pt C, p. 203-212Article in journal (Refereed)
  • 306.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    15N NMR chemical shift in the characterisation of halogen bonding in solution2017Conference paper (Refereed)
    Abstract [en]

    15N NMR chemical shift in the characterisation of halogen bonding in solution  

    Sebastiaan B. Hakkert, Jürgen Gräfenstein and Mate Erdelyi*   

    NMR chemical shift changes induced upon formation of non-covalent interactions have been used as sensitive and specific observables in the evaluation of weak chemical forces in solutions, among others of halogen bonding.1 1H NMR has high sensitivity yet a narrow chemical shift range, ca 10 ppm, resulting in small and thus difficult to measure chemical shift changes upon binding. In contrast, 13C NMR offers a wider shift range, ca 200 ppm, providing larger chemical shift changes upon weak binding to be detected; however, its low sensitivity limits its applicability. 19F NMR provides high sensitivity and a wide chemical shift range, ca 500 ppm, and hence is straightforwardly applicable on substances that possess a fluorine close to the halogen bond donor site,2 but is unfortunately often unavailable for real-life substances applied in medicinal chemistry, for example, typically missing fluorine substitution. 15N NMR despite its low sensitivity, which can be overcome by indirect detection experiments (HMBC), provides several advantages, such as an unusually wide chemical shift range, ca 900 ppm, and most importantly the detectability of halogen and hydrogen bonds directly at the Lewis base involved in the interaction. Accordingly, upon formation of a halogen bond with a nitrogen donor ligand typically 10-20 ppm,3 and for very strong interactions up to 100 ppm,4 15N chemical shift changes have been reported.  

    In this project we have evaluated the capability of 15N NMR to describe halogen bonding interactions with respect to solvent and electronic effects, and the alteration of N-X bond lengths. The observations made for halogen bonds were compared to those obtained for analogous hydrogen bonding systems using the same nitrogen donor halogen/hydrogen bond acceptor. The experimental data obtained on an 800 MHz spectrometer was compared to and interpreted with the help of computational data (DFT).The observed chemical shift changes upon formation of halogen bonds were correlated to various descriptors to understand their origin. Based on the above data the scope and limitations of 15N NMR for detection and understanding of halogen bonding in solution will be discussed.

    References

    1. Bertrán, J. F.; Rodríguez, M. Org. Magn. Reson. 1979, 12, 92, 1980, 14, 244; 1981, 16, 79.

    2. Metrangolo, P.; Panzeri, W.; Recupero F; Resnati, G. J. Fluorine Chem. 2002, 114, 27.

    3. Castro-Fernandez, S.; Lahoz, I. R.; Llamas-Saiz, A. L.; Alonso-Gomez, J. L.; Cid, M. M.; Navarro-Vazquez, A. Org. Lett. 2014, 16, 1136; Puttreddy, R.; Jurcek, O.; Bhowmik, S.; Makela, T.; Rissanen, K. Chem. Commun. 2016, 52, 2338.

    4. Carlsson, A.-C. C.; Grafenstein, J.; Budnjo, A.; Laurila, J. L.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706

  • 307.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Halogen and hydrogen bonding -: computationally supported NMR spectroscopy2017Conference paper (Refereed)
  • 308.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Halogen Bonding:: An Alternative Tool to Modulate Peptide Conformation2017Conference paper (Refereed)
    Abstract [en]

    Halogen bonding: an alternative tool to modulate peptide conformation

    Emma Danelius(1), Hanna Andersson(1), Patrik Jarvoll(1), Kajsa Lood(1), Jürgen Gräfenstein(1) and  Mate Erdelyi(1,2)

    1) Department of Chemistry and Molecular Biology, University of Gothenburg, Sweden

    2) Department of Chemistry – BMC, Uppsala University, Sweden   

    Halogen bonding is a weak chemical force that resembles hydrogen bonding in many aspects. Despite its potential for use in drug discovery, as a new molecular tool in the direction of molecular recognition events, it has so far rarely been assessed in biopolymers. Motivated by this fact, we have developed a peptide model system that permits the quantitative evaluation of weak forces in a biologically relevant proteinlike environment and have applied it for the assessment of a halogen bond formed between two amino acid side chains. 

    The influence of a single weak force is measured by detection of the extent to which it modulates the conformation of a cooperatively folding system. We have optimized the amino acid sequence of the model peptide on analogues with a hydrogen bond-forming site as a model for the intramolecular halogen bond to be studied, demonstrating the ability of the technique to provide information about any type of weak secondary interaction. 

    A combined solution nuclear magnetic resonance spectroscopic and computational investigation demonstrates that an interstrand halogen bond is capable of conformational stabilization of a β-hairpin foldamer comparable to an analogous hydrogen bond. This is the first report of incorporation of a conformation-stabilizing halogen bond into a peptide/protein system, and the first quantification of a chlorine-centered halogen bond in a biologically relevant system in solution.  

  • 309.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    ParLig:: Paramagnetic Ligand Tagging to Identify Protein Binding Sites2017Conference paper (Refereed)
    Abstract [en]

    ParLig: Paramagnetic Ligand Tagging to  Identify Protein Binding Sites

    Ulrika Brath,1 Shashikala I. Swamy,1 Alberte X. Veiga,1 Ching-Chieh Tung,2 Filip Van Petegem,2 Mate Erdelyi1*

    Department of Chemistry & Molecular Biology and the Swedish NMR Centre, University of Gothenburg,Sweden

    Department of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, Canada  

    Abstract: Identification of the binding site and binding mode of low affinity ligands, such as screening hits, is essential for the development of pharmaceutical leads using rational drug design strategies. We introduce ParLig, a paramagnetic ligand tagging approach that enables localization of protein – ligand binding clefts by detection and analysis of intermolecular protein NMR pseudocontact shifts, invoked by the covalent attachment of a paramagnetic lanthanoid chelating tag to the ligand of interest. Its scope is demonstrated by identification of the low mM volatile anesthetic interaction site of calmodulin. The technique provides an efficient route to rapid screening of protein – ligand systems, and to the identification of the binding site and mode of low affinity complexes.

    References: 

    1. Brath, U., Swami, S.I., Veiga, A.X., Tung, C.-C., Van Petegem, F., Erdelyi, M., J. Am. Chem Soc. 137, 11391-11398 (2015) .

  • 310.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Pentacoordinate carbonium ions in solution2018Conference paper (Refereed)
  • 311.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Solid-phase methods for the synthesis of heterocycles2006In: Microwave-Assisted  Synthesis of Heterocycles, Topics in Heterocyclic Chemistry, Berlin/Heidelberg, Germany: Springer GmbH & Co KB, Berlin/Heidelberg, Germany , 2006, p. 79-128Chapter in book (Refereed)
  • 312.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    The three-center halogen bond2019Conference paper (Refereed)
    Abstract [en]

    Halonium ions, X+, play important roles in chemistry. In halogenation reactions, they are transferred from a halogen donor, D, to an acceptor, A, in the formally stepwise process D+- X + A →[D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A]+→ [D∙∙∙X-A]  → D + X-A+. The same process takes place when a halogen moves from a halogen bond [1] acceptor to another one within a complex, that has so far mostly been studied in model systems with the two donor sites possessing comparable Lewis basicities (A ~ D) [2-5]. Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases, with the bonds having varying degrees of covalency and secondary character [2].  Halonium ions are strong halogen bond donors that prefer to form a three-center geometry, [D∙∙∙X∙∙∙D]+, in which both D-X halogen bonds have partial covalent and partial secondary characters [2-6].

    In this talk, the influence of electronic and steric factors, solvent polarity and counterions, and of the type of the halogen on the geometry and reactivity of [D∙∙∙X∙∙∙D]+ halogen bond complexes will be discussed. The symmetric state, [D∙∙∙X∙∙∙D]+, is demonstrated to be strongly preferred over the alternative asymmetric arrangements [D∙∙∙X-D]+. Understanding the three-center halogen bonds provides insights into the fundamentals of the halogen bonding phenomenon and of halonium transfer reactions. The studied complexes are isoelectronic to the transition state of SN2 reactions, and thus may provide model systems for the exploration of fundamental reaction mechanisms.

    The synthesis, and the NMR spectroscopic and computational (DFT) studies of a variety of three-center halogen bond systems [2-6] will be presented focusing on the influence of steric and electronic factors on the geometry and electronic character of the three-center-fourelectron halogen bond.

    References 1. Halogen bonding is the noncovalent interaction of halogen in which they act as electron acceptors. 2. Karim, A.; Reitti, M.; Carlsson, A.-C.C.; Gräfenstein, J.; Erdelyi, M. Chem. Sci. 2014, 5, 3226. 3. Carlsson, A.-C.C.; Mehmeti, K.; Uhrbom, M.; Karim, A.; Bedin, M.; Puttreddy, R.; Kleinmaier, R.; Neverov, A.; Nekoueishahraki, B.; Gräfenstein, J.; Rissanen, K.; Erdelyi, M., J. Am. Chem. Soc. 2016, 138, 9853. 4. Carlsson, A.-C.C.; Gräfenstein,J.; Budnjo, A.; Bergquist, J.; Karim, A.; Kleinmaier, R.; Brath, U.; Erdelyi, M. J. Am. Chem. Soc. 2012, 134, 5706.  5. Hakkert, S.B.; Erdelyi, M. J. Phys. Org. Chem. 2015, 28, 226. 6.Lindblad, S.; Mehmeti, K.; Veiga, A.; Nekoueishahraki, B.; Gräfenstein, J.; Erdelyi, M. J. Am. Chem. Soc.2018, 140, 13503.

  • 313.
    Erdélyi, Máté
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    The three-centered halogen bond2018Conference paper (Refereed)
  • 314.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    d’Auvergne, E.
    Navarro-Vazquez, A.
    Griesinger, C.
    Dynamics of the glycosidic linkage: conformational space of lactose2011In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 17, no 34, p. 9368-9376Article in journal (Refereed)
    Abstract [en]

    The dynamics of the glycosidic bond of lactose was studied by a paramagnetic tagging‐based NMR technique, which allowed the collection of an unusually large series of NMR data for a single compound. By the use of distance‐ and orientation‐dependent residual dipolar couplings and pseudocontact shifts, the simultaneous fitting of the probabilities of computed conformations and the orientation of the magnetic susceptibility tensor of a series of lanthanide complexes of lactose show that its glycosidic bond samples syn/syn, anti/syn and syn/anti ϕ/ψ regions of the conformational space in water. The analysis indicates a higher reliability of pseudocontact shift data as compared to residual dipolar couplings with the presently available weakly orienting paramagnetic tagging technique. The method presented herein allows for an improved understanding of the dynamic behaviour of oligosaccharides.

  • 315.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Gogoll, Adolf
    Rapid Microwave-assisted solid-phase peptide synthesis2003Conference paper (Refereed)
  • 316.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Gogoll, Aldof
    Development of a stilbene-type photoswitchable β-hairpin mimetic2005Conference paper (Refereed)
  • 317.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Karlén, A.
    Gogoll, Aldolf
    Studies of Photoswitchable β-Hairpin Mimetics2003Conference paper (Refereed)
  • 318.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Langer, V.
    Karlén, A.
    Gogoll, Adolf
    Structural Studies of Diastereomeric β-Hairpin Mimetics2002Conference paper (Refereed)
  • 319.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Lindblad, Sofia
    Mehmeti, Krenare
    Veiga, Alberte X
    Nekoueishahraki, Bijan
    Gräfenstein, Jurgen
    The Halogen Bond of Halonium Ions2018Conference paper (Refereed)
    Abstract [en]

    Halonium ions, X+ , play important roles in chemistry. In halogenation reactions, they are transferred from a donor, D, to an acceptor, A, in the formally stepwise process D-X + A

    → [D-X∙∙∙A]+ → [D∙∙∙X∙∙∙A][D∙∙∙X - A]+ → D + X - A+. The same process takes place when a halogen moves from a halogen bond donor to an acceptor within a complex, which has been studied so far mostly in model systems in which the donor and the acceptor possess comparable Lewis basicities (A ~ D) [1-4].  Throughout these processes the halonium ion simultaneously forms bonds to two Lewis bases that may possess varying degrees of covalency and secondary character [1]. Halonium ions are strong halogen bond donors that prefer to form a symmetric geometry, [D∙∙∙X∙∙∙D]+, with two D-X bonds of partial covalent and partial secondary character. This symmetric state is much preferred over the asymmetric alternative arrangement, [D∙∙∙X - D]+[1-4].

    We have explored how electronic and steric factors influence the electron density distribution and the geometry of [D∙∙∙X∙∙∙D]+-type complexes. Understanding this provides insights into the fundamental details of halonium transfer reactions, halogen transfer processes within halogen bonded systems as well as into important reaction mechanisms, such as SN2.

    In this talk the synthesis, NMR spectroscopic and computational (DFT) studies of so far undiscussed systems [5] will be presented, and the influence of steric and electronic factors on the geometry and electronic character of the three-center-four-electron halogen bond will be discussed.

  • 320.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Navarro-Vázquez, Armando
    Pfeiffer, Bernhard
    Kuzniewski, Christian N
    Felser, Andrea
    Widmer, Toni
    Gertsch, Jürg
    Pera, Benet
    Díaz, José Fernando
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    The binding mode of side chain- and C3-modified epothilones to tubulin2010In: ChemMedChem, ISSN 1860-7179, E-ISSN 1860-7187, Vol. 5, no 6, p. 911-920Article in journal (Refereed)
    Abstract [en]

    The tubulin-binding mode of C3- and C15-modified analogues of epothilone A (Epo A) was determined by NMR spectroscopy and computational methods and compared with the existing structural models of tubulin-bound natural Epo A. Only minor differences were observed in the conformation of the macrocycle between Epo A and the C3-modified analogues investigated. In particular, 3-deoxy- (compound 2) and 3-deoxy-2,3-didehydro-Epo A (3) were found to adopt similar conformations in the tubulin-binding cleft as Epo A, thus indicating that the 3-OH group is not essential for epothilones to assume their bioactive conformation. None of the available models of the tubulin-epothilone complex is able to fully recapitulate the differences in tubulin-polymerizing activity and microtubule-binding affinity between C20-modified epothilones 6 (C20-propyl), 7 (C20-butyl), and 8 (C20-hydroxypropyl). Based on the results of transferred NOE experiments in the presence of tubulin, the isomeric C15 quinoline-based Epo B analogues 4 and 5 show very similar orientations of the side chain, irrespective of the position of the nitrogen atom in the quinoline ring. The quinoline side chain stacks on the imidazole moiety of beta-His227 with equal efficiency in both cases, thus suggesting that the aromatic side chain moiety in epothilones contributes to tubulin binding through strong van der Waals interactions with the protein rather than hydrogen bonding involving the heteroaromatic nitrogen atom. These conclusions are in line with existing tubulin polymerization and microtubule-binding data for 4, 5, and Epo B.

  • 321.
    Erdélyi, Máté
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Organic Chemistry.
    Pfeiffer, Bernhard
    Hauenstein, Kurt
    Fohrer, Jörg
    Gertsch, Jürg
    Altmann, Karl-Heinz
    Carlomagno, Teresa
    Conformational preferences of natural and C3-modified epothilones in aqueous solution.2008In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 51, no 5, p. 1469-73Article in journal (Refereed)
    Abstract [en]

    The conformational properties of the microtubule-stabilizing agent epothilone A ( 1a) and its 3-deoxy and 3-deoxy-2,3-didehydro derivatives 2 and 3 have been investigated in aqueous solution by a combination of NMR spectroscopic methods, Monte Carlo conformational searches, and NAMFIS calculations. The tubulin-bound conformation of epothilone A ( 1a), as previously proposed on the basis of solution NMR data, was found to represent a significant fraction of the ensemble of conformations present for the free ligands in aqueous solution.

  • 322.
    Ericsson, Maria
    et al.
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Fallahsharoudi, Amir
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. ARUP Institute for Clinical & Experimental Pathology, Salt Lake City, UT, USA AND Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
    Kushnir, Mark M.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. ARUP Institute for Clinical & Experimental Pathology, Salt Lake City, UT, USA AND Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
    Jensen, Per
    AVIAN Behavioural Genomics and Physiology Group, IFM Biology, Linköping University, 58183 Linköping, Sweden.
    Domestication effects on behavioural and hormonal responses to acute stress in chickens2014In: Physiology and Behavior, ISSN 0031-9384, E-ISSN 1873-507X, Vol. 133, p. 161-169Article in journal (Refereed)
    Abstract [en]

    Comparative studies have shown that alterations in physiology, morphology and behaviour have arisen due to the domestication. A driving factor behind many of the changes could be a shift in stress responses, with modified endocrine and behavioural profiles. In the present study we compared two breeds of chicken (Gallus gallus), the domestic White Leghorn (WL) egg laying breed and its ancestor, the Red Junglefowl (RJF). Birds were exposed to an acute stress event, invoked by 3 or 10 min of physical restraint. They were then continuously monitored for the effects on a wide range of behaviours during a 60 min recovery phase. Blood samples were collected from the chicken at baseline, and after 10 and 60 min following a similar restraint stress, and the samples were analyzed for nine endogenous steroids of the HPA and HPG axes. Concentration of the steroids was determined using validated liquid chromatography tandem mass spectrometry methods. In RJF, an immediate behavioural response was observed after release from restraint in several behaviours, with a relatively fast return to baseline within 1 h. In WL, some behaviours were affected for a longer period of time, and others not at all. Concentrations of corticosterone increased more in RJF, but returned faster to baseline compared to WL. A range of baseline levels for HPG-related steroids differed between the breeds, and they were generally more affected by the stress in WL than in RJF. In conclusion, RJF reacted stronger both behaviourally and physiologically to the restraint stress, but also recovered faster. This would appear to be adaptive under natural conditions, whereas the stress recovery of domesticated birds has been altered by domestication and breeding for increased reproductive output.

  • 323. Ericzon, Christina
    et al.
    Pettersson, Jean
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University.
    Olin, Åke
    Interference from iodide in the determination of trace level selenium1990In: Talanta: The International Journal of Pure and Applied Analytical Chemistry, ISSN 0039-9140, E-ISSN 1873-3573, Vol. 37, no 7, p. 725-730Article in journal (Refereed)
    Abstract [en]

    The rate of the reaction between iodide and selenium(IV) at trace levels to form selenium and iodine has been determined in 1–6M hydrochloric acid. The reaction rate increases rapidly with acidity. When hydrochloric acid is added to reduce selenate to selenite prior to the determination of total selenium, some selenium may be lost by reduction to the element if iodide is present. A table of half-lives of the selenite—iodide reaction under various conditions is presented. A method for removal of iodide is suggested.

  • 324.
    Erik, Gioeli
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Biochemistry.
    Utbytesoptimering inom läkemedelsproduktion: Identifiering av kassationsorsaker inom AstraZenecas packningsprocess i Gärtuna2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    The project aimed to deliver recommendations of how to optimize the yield of thepackaging process of tablets and capsules within AstraZeneca's facility in Gärtuna(Södertälje), Sweden. The project scope included nine packaging lines of blisterproducts with highly similar process steps. The crucial part of the puzzle was toidentify cassation sources within these production lines, which was achieved by thecombined methology of qualitative interviews, quantitative surveys and statisticalprocess control applied to logged production data.The following cassation sources were identified:- Cassation as a side effect of start-up controls within an order- Safety cassation of tablets when the blister machine stops- In many cases, the safety cassation also occours when the cartoner stops- A cut-in-half tablet causing cassation of multiple tablets in the rejection steps- Leftover product on the packaging line when the order is finished- Target conflict between high productivity of the production line and high yield withinthe order- Difficulty optimizing machines settings for small order sizes, leading to higher stopfrequency and therefore more safety cassation of tablets, as well as a higher risk thattablets are sorted out in control stepsWhich led to these recommendations:- Optimizing the yield as a target value for process optimization- Log the yield for all the process steps within the packaging line- Consider the possibility of reintroducing rejected blisters containing approvedtablets- Clear prioritization of the target conflict between high productivity and high yield- Analyze if there are any time-consuming steps conflicting with high yield within theprocess of closing an order which are not required to be performed at that particularprocess stepAs well as future work:- Get to the bottom of the correlation between low yield and small order sizes- Investigate further which materials are prone to cause machine stops within thecartoner- Dig deeper into the problem of cut-in-half tablets existing pre-packaging-process

  • 325.
    Eriksson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bartsch, Maik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Bergström Lind, Sara
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, no SI, p. 105-109Article in journal (Refereed)
    Abstract [en]

    A recently developed titanium dioxide (TiO2) based on-target method for phosphopeptide enrichment and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS) analysis was used to investigate phosphorylations in the Adenovirus type 2 structural protein pIIIa. Lysates of purified virus particles were separated on 1-D SDS-PAGE and the band for the pIIIa protein was excised for tryptic digestion into peptides that were enriched with the on-target method. The enrichment provided by the method clearly improved the detectability of phosphorylated peptides and the results show for the first time evidence for multi-phosphorylated peptides in pIIIa. Moreover, three novel phosphorylations were identified in the protein sequence, even though the precise positions could not be determined. These results illustrate the potential of the method for the characterization of novel phosphoproteomes in biological samples of medical relevance.

  • 326.
    Eriksson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Cooperative adsorption behavior of phosphopeptides on TiO2 leads to biased enrichment, detection and quantification2015In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 140, no 1, p. 303-312Article in journal (Refereed)
    Abstract [en]

    The adsorption behavior of phosphopeptides onto TiO2 surfaces was studied using the quartz crystal microbalance with dissipation monitoring (QCM-D) as the main experimental technique. The main focus is the characterization of the emergence of positive cooperativity under conditions where the peptides have a positively charged C-term. It is shown that when carrying no net charge, small water-soluble peptides as a rule develop positive cooperativity. The impact of the adsorption mechanism on the outcome of TiO2 based enrichment methods was investigated with the help of matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS). The data presented illustrate how the phosphopeptide profile in the enriched material may deviate from that in the native sample, as cooperative phosphopeptides are overrepresented in the former. Furthermore, commonly employed washing and elution solutions may facilitate preferential release of certain peptides, leading to further bias in the recovered sample. Taken together, the results of the present study demonstrate that thorough understanding of the mechanisms behind the adsorption of phosphopeptides on the enrichment material is necessary in order to develop reliable qualitative and quantitative methods for phosphoproteomics.

  • 327.
    Eriksson, Anna
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Hagfeldt, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique2013In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 7, p. 2019-2025Article in journal (Refereed)
    Abstract [en]

    The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2–phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.

  • 328.
    Eriksson, Anna I. K.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Enrichment and Separation of Phosphorylated Peptides on Titanium Dioxide Surfaces: Applied and Fundamental Studies2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Protein phosphorylation is a very common posttranslational modification (PTM), which lately has been found to hold the keyrole in the development of many severe diseases, including cancer. Thereby, phosphoprotein analysis tools, generally based on specific enrichment of the phosphoryl group, have been a hot topic during the last decade.

    In this thesis, two new TiO2-based on-target enrichment methods are developed and presented together with enlightening fundamental results.

    Evaluation of the developed methods was performed by the analysis of: custom peptides, β-casein, drinking milk, and the viral protein pIIIa. The results show that: i) by optimizing the enrichment protocol (first method), new phosphorylated peptides can be found and ii) by the addition of a separation step after the enrichment (second method), more multi-phosphorylated peptides, which usually are hard to find, could be detected. The fundamental part, on the other hand, shows that the phosphopeptide adsorption is caused by electrostatic interactions, in general follows the Langmuir model, and the affinity increases with the phosphorylation degree. Here, however, the complexity of the system was also discovered, as the adsorption mechanism was found to be affected by the amino acid sequence of the phosphopeptide.

    List of papers
    1. Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide
    Open this publication in new window or tab >>Optimized Protocol for On-Target Phosphopeptide Enrichment Prior to Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry Using Mesoporous Titanium Dioxide
    Show others...
    2010 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 82, no 11, p. 4577-4583Article in journal (Refereed) Published
    Abstract [en]

    A novel on-target phosphopeptide enrichment method is presented that allows specific enrichment and direct analysis by matrix assisted laser desorption-ionization mass spectrometry (MALDI-MS) of phosphorylated peptides. Spots consisting of a thin film of anatase titanium dioxide are sintered onto a conductive glass surface. Enrichment and analysis can be performed on the modified target with minimal sample handling. The protocol leads to an enrichment efficiency that is superior to what has been reported before for similar methods. The method was tested using beta-casein as a model phosphorylated protein as well as with a custom peptide mixed with its phosphorylated form. A very low detection limit, a significantly improved phosphoprofiling capability, and a simple experimental approach provide a powerful tool for the enrichment, detection, and analysis of phosphopeptides.

    National Category
    Chemical Sciences
    Research subject
    Chemistry
    Identifiers
    urn:nbn:se:uu:diva-125767 (URN)10.1021/ac100589j (DOI)000278062800040 ()20443553 (PubMedID)
    Available from: 2010-05-31 Created: 2010-05-28 Last updated: 2017-12-12Bibliographically approved
    2. Mesoporous TiO2-Based Experimental Layout for On-Target Enrichment and Separation of Multi- and Monophosphorylated Peptides Prior to Analysis with Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Open this publication in new window or tab >>Mesoporous TiO2-Based Experimental Layout for On-Target Enrichment and Separation of Multi- and Monophosphorylated Peptides Prior to Analysis with Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
    Show others...
    2011 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 83, no 3, p. 761-766Article in journal (Refereed) Published
    Abstract [en]

    A simple method for on-target enrichment and subsequent separation and analysis of phosphorylated peptides is presented. The tryptic digest of a phosphorylated protein, in this case beta-casein, is loaded onto a spot on a thin stripe made of mesoporous TiO2 sintered onto a conductive glass surface. After washing with a salicylic buffer in order to remove the nonphosphorylated peptides, the stripe is placed in an elution chamber containing a phosphate solution. In a way analogous to thin layer chromatography (TLC), the phosphate solution acts as an eluent, clearly separating multi- and monophosphorylated peptides. By performing matrix-assisted laser desorption-ionization mass spectrometry (MALDI-MS) along the stripe, the detection of all phosphorylated peptides present in the digest is facilitated, as they are isolated from each other. The method was also tested on commercial drinking milk, achieving successful separation between multi- and monophosphorylated peptides, as well as a detection limit in the femtomole range. As the enrichment, separation, and analysis take place in the same substrate, sample handling and risk of contamination and sample loss is minimized. The results obtained suggest that the method, once optimized, may successfully provide a complete phosphoproteome.

    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-148662 (URN)10.1021/ac1027879 (DOI)000286689600021 ()21210638 (PubMedID)
    Available from: 2011-03-09 Created: 2011-03-09 Last updated: 2017-12-11Bibliographically approved
    3. Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique
    Open this publication in new window or tab >>Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique
    2013 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 7, p. 2019-2025Article in journal (Refereed) Published
    Abstract [en]

    The rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2–phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.

    Place, publisher, year, edition, pages
    American Chemical Society (ACS), 2013
    National Category
    Physical Chemistry
    Research subject
    Chemistry with specialization in Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-195262 (URN)10.1021/jp310161m (DOI)000315432200004 ()
    Available from: 2013-02-22 Created: 2013-02-22 Last updated: 2017-12-06Bibliographically approved
    4. On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein
    Open this publication in new window or tab >>On-target titanium dioxide-based enrichment for characterization of phosphorylations in the Adenovirus pIIIa protein
    Show others...
    2013 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1317, no SI, p. 105-109Article in journal (Refereed) Published
    Abstract [en]

    A recently developed titanium dioxide (TiO2) based on-target method for phosphopeptide enrichment and matrix assisted laser desorption-ionization mass spectrometry (MALDI MS) analysis was used to investigate phosphorylations in the Adenovirus type 2 structural protein pIIIa. Lysates of purified virus particles were separated on 1-D SDS-PAGE and the band for the pIIIa protein was excised for tryptic digestion into peptides that were enriched with the on-target method. The enrichment provided by the method clearly improved the detectability of phosphorylated peptides and the results show for the first time evidence for multi-phosphorylated peptides in pIIIa. Moreover, three novel phosphorylations were identified in the protein sequence, even though the precise positions could not be determined. These results illustrate the potential of the method for the characterization of novel phosphoproteomes in biological samples of medical relevance.

    Keywords
    Phosphopeptide enrichment, MALDI-MS, Separation, Capsid protein precursor pIIIa, TiO2
    National Category
    Analytical Chemistry Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-204683 (URN)10.1016/j.chroma.2013.08.096 (DOI)000327229600012 ()
    Available from: 2013-08-09 Created: 2013-08-08 Last updated: 2017-12-06Bibliographically approved
  • 329.
    Eriksson, Barbro
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Örlefors, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundin, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Skogseid, Britt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Bergström, Anders
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Positron emission tomography in neuroendocrine tumors1999In: The Italian Journal of Gastroenterology and Hepatology, ISSN 1125-8055, Vol. 31, p. 167-171Article in journal (Refereed)
  • 330.
    Eriksson, Emma
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Production of HIV-1 protease for nuclear magnetic resonance studies2013Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 331.
    Eriksson, Emma K.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Effects of Ubiquinone-10 on the Stability and Mechanical Properties of Lipid Membranes2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Ubiquinones are a group of fat-soluble molecules present in many biological membranes. The most abundant version in humans, ubiquinone-10 (Q10), plays an important role in the mitochondrial respiration chain and also functions as a powerful antioxidant. Accumulating evidence suggests that Q10 also could have other functions in the membrane. The aim of this thesis has been to explore Q10’s possible role as a membrane stabilizer.

    To investigate the potential effect of Q10 in membranes, liposomes with compositions of biological relevance were used as models systems. In lipid systems mimicking that of the inner membrane of the mitochondria, Q10 was found to lower the membrane’s permeability to hydrophilic solutes, render the membrane more resistant to rupturing and promote membrane lipid order. In models mimicking the plasma membrane of E.coli, Q10 was observed to decrease the water permeability and increase the elastic resistance against membrane deformation during osmotic shock. All in all, the results suggest a general membrane stabilizing effect of Q10. The results indicate, however, that the extent of, as well as the mechanisms behind, the membrane stabilizing effects of Q10 vary depending on the membrane lipid composition. Part of the reason for this can likely be traced back to differences in the intermembrane location of Q10.

    Supplementary experiments, which facilitated the investigations of Q10 membrane effects, revealed that the choice of cuvette material was of importance for liposome leakage experiments with fluorescent hydrophilic dyes. The results of these experiments highlight the need to take liposome-cuvette interactions into account when planning and evaluating spectroscopic studies involving liposomes.

    List of papers
    1. Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes
    Open this publication in new window or tab >>Ubiquinone-10 alters mechanical properties and increases stability of phospholipid membranes
    2015 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1848, no 10, p. 2233-2243Article in journal (Refereed) Published
    Abstract [en]

    Abstract Ubiquinone-10 is mostly known for its role as an electron and proton carrier in aerobic cellular respiration and its function as a powerful antioxidant. Accumulating evidence suggest, however, that this well studied membrane component could have several other important functions in living cells. The current study reports on a previously undocumented ability of ubiquinone-10 to modulate the mechanical strength and permeability of lipid membranes. Investigations of DPH fluorescence anisotropy, spontaneous and surfactant induced leakage of carboxyfluorescein, and interactions with hydrophobic and hydrophilic surfaces were used to probe the effects caused by inclusion of ubiquinone-10 in the membrane of phospholipid liposomes. The results show that ubiquinone in concentrations as low as 2 mol.% increases the lipid packing order and condenses the membrane. The altered physicochemical properties result in a slower rate of release of hydrophilic components, and render the membrane more resistant towards rupture. As judged from comparative experiments using the polyisoprenoid alcohol solanesol, the quinone moiety is essential for the membrane stabilizing effects to occur. Our findings imply that the influence of ubiquinone-10 on the permeability and mechanical properties of phospholipid membranes is similar to that of cholesterol. The reported data indicate, however, that the molecular mechanisms are different in the two cases.

    Keywords
    Coenzyme Q10, Liposomes, Leakage, Membrane stability, Solanesol
    National Category
    Chemical Sciences
    Identifiers
    urn:nbn:se:uu:diva-253627 (URN)10.1016/j.bbamem.2015.05.002 (DOI)000362153400032 ()
    Funder
    Swedish Research Council, 621-2011-3524Swedish Cancer Society, CAN20111504
    Available from: 2015-05-29 Created: 2015-05-29 Last updated: 2018-09-23Bibliographically approved
    2. Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.
    Open this publication in new window or tab >>Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.
    2018 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1860, no 5, p. 1205-1215Article in journal (Refereed) Published
    Abstract [en]

    Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing function. In line with this, we showed in a previous study that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) membranes. In the current study we report on the effects exerted by Q10 in membranes having a more complex lipid composition designed to mimic that of the inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and permeability measurements, as well as investigations probing the interaction of liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10 also in the IMM-mimicking membranes. Comparative investigations examining the effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on membranes composed of individual IMM components suggest, moreover, that Q10 improves the membrane barrier properties via different mechanisms depending on the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on CF release from pure POPC membranes appears to be directly and solely related to Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability to amplify intrinsic curvature elastic stress dominates in case of membranes containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE).

    Keywords
    Biomimetic membranes, Coenzyme Q10, Liposomes, Membrane stability, Solanesol
    National Category
    Biophysics
    Identifiers
    urn:nbn:se:uu:diva-353473 (URN)10.1016/j.bbamem.2018.02.015 (DOI)000435057700029 ()29470946 (PubMedID)
    Funder
    Swedish Research Council, 2016-03464Swedish Cancer Society, 17 0566
    Available from: 2018-06-13 Created: 2018-06-13 Last updated: 2018-09-23Bibliographically approved
    3. Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane
    Open this publication in new window or tab >>Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane
    Show others...
    2019 (English)In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1861, no 7, p. 1388-1396Article in journal (Refereed) Published
    Abstract [en]

    Bacteria need to be able to adapt to sudden changes in their environment, including drastic changes in the surrounding osmolarity. As part of this adaptation, the cells adjust the composition of their cytoplasmic membrane. Recent studies have shown that ubiquinones, lipid soluble molecules involved in cell respiration, are overproduced by bacteria grown in hyperosmotic conditions and it is thus believed that these molecules can provide with osmoprotection. Hereby we explore the mechanisms behind these observations. Liposomes with a lipid headgroup composition mimicking that of the cytoplasmic membrane of E. coli are used as suitable models. The effect of ubiquinone-10 (Q10) on water transport across the membranes is characterized using a custom developed fluorescence-based experimental approach to simultaneously determine the membrane permeability coefficient and estimate the elastic resistance of the membrane towards deformation. It is shown that both parameters are affected by the presence of ubiquinone-10. Solanesol, a molecule similar to Q10 but lacking the quinone headgroup, also provides with osmoprotection although it only improves the resistance of the membrane against deformation. The fluorescence experiments are complemented by cryogenic transmission electron microscopy studies showing that the E. coli membrane mimics tend to flatten into spheroid oblate structures when osmotically stressed, suggesting the possibility of lipid segregation. In agreement with its proposed osmoprotective role, the flattening process is hindered by the presence of Q10.

    Keywords
    Coenzyme Q10, Liposomes, Membrane elasticity, Osmotic stress, Solanesol, Water permeability
    National Category
    Analytical Chemistry
    Research subject
    Chemistry with specialization in Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-361360 (URN)10.1016/j.bbamem.2019.04.008 (DOI)000474325100012 ()31026443 (PubMedID)
    Funder
    Swedish Research Council, 2016-03464Swedish Cancer Society, 17 0566
    Available from: 2018-09-23 Created: 2018-09-23 Last updated: 2019-09-17Bibliographically approved
    4. Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.
    Open this publication in new window or tab >>Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.
    2018 (English)In: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 215, p. 63-70, article id S0009-3084(18)30129-4Article in journal (Refereed) Published
    Abstract [en]

    Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.

    Keywords
    Carboxyfluorescein, Fluorescence, Polystyrene cuvettes, QCM-D, Quartz cuvettes, Spontaneous leakage
    National Category
    Biophysics Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-357926 (URN)10.1016/j.chemphyslip.2018.07.006 (DOI)000443661800008 ()30076799 (PubMedID)
    Available from: 2018-08-22 Created: 2018-08-22 Last updated: 2018-11-08Bibliographically approved
  • 332.
    Eriksson, Emma K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernandez, Victor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Effect of ubiquinone-10 on the stability of biomimetic membranes of relevance for the inner mitochondrial membrane.2018In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1860, no 5, p. 1205-1215Article in journal (Refereed)
    Abstract [en]

    Ubiquinone-10 (Q10) plays a pivotal role as electron-carrier in the mitochondrial respiratory chain, and is also well known for its powerful antioxidant properties. Recent findings suggest moreover that Q10 could have an important membrane stabilizing function. In line with this, we showed in a previous study that Q10 decreases the permeability to carboxyfluorescein (CF) and increases the mechanical strength of 1-palmitoyl-2-oleyl-sn-glycero-phosphocholine (POPC) membranes. In the current study we report on the effects exerted by Q10 in membranes having a more complex lipid composition designed to mimic that of the inner mitochondrial membrane (IMM). Results from DPH fluorescence anisotropy and permeability measurements, as well as investigations probing the interaction of liposomes with silica surfaces, corroborate a membrane stabilizing effect of Q10 also in the IMM-mimicking membranes. Comparative investigations examining the effect of Q10 and the polyisoprenoid alcohol solanesol on the IMM model and on membranes composed of individual IMM components suggest, moreover, that Q10 improves the membrane barrier properties via different mechanisms depending on the lipid composition of the membrane. Thus, whereas Q10's inhibitory effect on CF release from pure POPC membranes appears to be directly and solely related to Q10's lipid ordering and condensing effect, a mechanism linked to Q10's ability to amplify intrinsic curvature elastic stress dominates in case of membranes containing high proportions of palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE).

  • 333.
    Eriksson, Emma K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Choice of cuvette material can influence spectroscopic leakage and permeability experiments with liposomes.2018In: Chemistry and Physics of Lipids, ISSN 0009-3084, E-ISSN 1873-2941, Vol. 215, p. 63-70, article id S0009-3084(18)30129-4Article in journal (Refereed)
    Abstract [en]

    Liposome solute permeability experiments are widely performed to gain information about lipid membrane characteristics. Spectroscopic methods are often used for this purpose, usually monitoring the leakage of a self-quenching fluorescent dye (e.g., carboxyfluorescein, CF) from the liposomes. Hereby, we investigate the effect of liposome-cuvette interactions, a seldom considered detail, on the results obtained from liposomal permeability experiments. The spontaneous leakage of CF from liposomes with different surface properties and phase states is followed using quartz and polystyrene cuvettes, and the results are compared. It is shown that for most lipid compositions the leakage profiles vary notably between different cuvette materials. Reproducibility of the measurements also varies depending on the cuvettes used, with polystyrene providing with more robust results. To explain these observations, the interaction of liposomes with polystyrene and quartz-like surfaces was characterized with the help of the quartz crystal microbalance with dissipation monitoring (QCM-D). Our results show that, while liposomes seldom interact with polystyrene, quartz-liposome interactions are almost unavoidable and have a large impact on the leakage experiments mainly via two mechanisms: i) the rupturing of liposomes on the cuvette surface causing a fast release of encapsulated CF, and ii) the disruption of adsorbed liposomes caused by magnetic stirring. Depending on their composition, the liposomes interact in different ways with quartz, affecting thus the extent of each proposed mechanism. The experiments demonstrate the importance of considering the cuvette material when planning and conducting spectroscopic experiments with liposomes.

  • 334.
    Eriksson, Emma K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grad, Philipp
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernandez, Victor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane2019In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, no 7, p. 1388-1396Article in journal (Refereed)
  • 335.
    Eriksson, Emma K.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Edwards, Katarina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Grad, Philipp
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gedda, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Agmo Hernández, Víctor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Osmoprotective effect of ubiquinone in lipid vesicles modelling the E. coli plasma membrane2019In: Biochimica et Biophysica Acta - Biomembranes, ISSN 0005-2736, E-ISSN 1879-2642, Vol. 1861, no 7, p. 1388-1396Article in journal (Refereed)
    Abstract [en]

    Bacteria need to be able to adapt to sudden changes in their environment, including drastic changes in the surrounding osmolarity. As part of this adaptation, the cells adjust the composition of their cytoplasmic membrane. Recent studies have shown that ubiquinones, lipid soluble molecules involved in cell respiration, are overproduced by bacteria grown in hyperosmotic conditions and it is thus believed that these molecules can provide with osmoprotection. Hereby we explore the mechanisms behind these observations. Liposomes with a lipid headgroup composition mimicking that of the cytoplasmic membrane of E. coli are used as suitable models. The effect of ubiquinone-10 (Q10) on water transport across the membranes is characterized using a custom developed fluorescence-based experimental approach to simultaneously determine the membrane permeability coefficient and estimate the elastic resistance of the membrane towards deformation. It is shown that both parameters are affected by the presence of ubiquinone-10. Solanesol, a molecule similar to Q10 but lacking the quinone headgroup, also provides with osmoprotection although it only improves the resistance of the membrane against deformation. The fluorescence experiments are complemented by cryogenic transmission electron microscopy studies showing that the E. coli membrane mimics tend to flatten into spheroid oblate structures when osmotically stressed, suggesting the possibility of lipid segregation. In agreement with its proposed osmoprotective role, the flattening process is hindered by the presence of Q10.

  • 336.
    Eriksson, Louise
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Method development and optimization for determination of lipid oxidation in emulsions2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Lipid emulsions in parenteral nutrition’s consist of two immiscible liquids described as oil in water phase. The oils in the emulsions can start to oxidize and make it become rancid. The oxidation can be measured for peroxide value, anisidine value and for free fatty acids (FFAs) as primary- and secondary oxidation products.

    This master thesis presents an analytical method used for analysis of oxidation products. The aim of this project was to come up with a method to separate the oil from the water-phase, to a sufficient yield and as pure as possible for analysis in a spectrophotometer called FoodLab fat. During the way experiments regarding stability of oils and finally a stability study on emulsions were done.

    Starting the separation experiments with ethanol to break the emulsion, this turned out to be the best way to go. Further investigation through extractions with 2- propanol/isooctane and ethanol/heptane were tested. The method needed to be simple, easy to use and not too time-consuming but still be repeatable and reliable.

    To optimize the separation, different centrifugation volumes, forces and times were tested. The results showed that in order to get the best separation the centrifugation volume and force cannot be too large or too small.

    The final method proved to be successful for the use as research method and to be able to see trends of oxidation for the products. Further research and validation of the instrument and the method needs to be done before it can be used as a quality control method. 

  • 337.
    Eriksson, Malin
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    The Establishment of a Small Challenger Company in a Segmented High-Technology Life Science Market: Challenges and Opportunities - a Model Case Study2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

     This study aims to identify the challenges and opportunities of a small challenger

    company in a rigid and conservative high technology life science market. Strategies

    for finding a foothold, establish a position and creating a viable company is

    discussed. Qualitative and quantitative data was collected through interviews,

    online survey and conjoint analysis which were used as market research tools. For

    an entrepreneurial firm in the life science market it is important to tend to their most

    valuable resource, the employees, and it is vital that they have an extensive

    knowledge of the market that they are active in. Strategic planning tools and

    templates aid in executing and implementing the proposed business model.

    Recommendations for a model case entrepreneurial company regarding continued

    market research, increasing sales and strategies for marketing are made. Included

    in the thesis is also a discussion of wall effects in HPLC and ways to counteract

    them.