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Bergström, Maria
Publications (10 of 21) Show all publications
Bergström, M., Ganji, S., Naidu Veluru, R. & Unelius, C. R. (2017). N-Iodosuccinimide (NIS) in Direct Aromatic Iodination. European Journal of Organic Chemistry (22), 3234-3239
Open this publication in new window or tab >>N-Iodosuccinimide (NIS) in Direct Aromatic Iodination
2017 (English)In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 22, p. 3234-3239Article in journal (Refereed) Published
Abstract [en]

N-Iodosuccinimide (NIS) in pure trifluoroacetic acid (TFA) offers a time-efficient and general method for the iodination of a wide range of mono-and disubstituted benzenes at room temperature, as demonstrated in this paper. The starting materials were generally converted into mono-iodinated products in less than 16 hours at room temperature, without byproducts. A few deactivated substrates needed addition of sulfuric acid to increase the reaction rate. Another exception was methoxybenzenes that preferentially were iodinated by NIS in acetonitrile with only catalytic amounts of TFA.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2017
Keywords
Iodine-mediated reactions, Regioselectivity, Iodination, Electrophilic substitution, Arenes
National Category
Organic Chemistry
Research subject
Chemistry, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-66906 (URN)10.1002/ejoc.201700173 (DOI)000403682000014 ()2-s2.0-85020488886 (Scopus ID)
Available from: 2017-07-14 Created: 2017-07-14 Last updated: 2019-08-29Bibliographically approved
Boman, S., Bergström, M., Blücher, A., Håkansson, A. & Andersson, H. S. (2016). Dietary habits of Swedish university students in nutrition science between 2001 and 2016. In: Abstracts. The 11th NORDIC NUTRITION CONFERENCE NNC2016. “Bridging nutrition sciences for better health in the Nordic countries”: . Paper presented at 11th Nordic Nutrition Conference, June 20-22, Gothenburg. , Article ID P470.
Open this publication in new window or tab >>Dietary habits of Swedish university students in nutrition science between 2001 and 2016
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2016 (English)In: Abstracts. The 11th NORDIC NUTRITION CONFERENCE NNC2016. “Bridging nutrition sciences for better health in the Nordic countries”, 2016, article id P470Conference paper, Poster (with or without abstract) (Other academic)
Abstract [en]

While the Swedish nutrition recommendations have been kept relatively constant in recent years, public attitudes to different diets have been swinging faster. The National food survey (Riksmaten), being performed in Sweden only once per decade, cannot identify any corresponding rapid changes in diets. Hence, our understanding of potential fluctuations is limited. During the last 15 years, nutrition students at the Linnaeus University (formerly University of Kalmar) have reported their food intake in the context of the course Diet, Nutrition and Health 7,5 hp. The result is an extensive data set comprising more than 1100 individuals and over 2500 days of food intake reports, and although not originally intended or designed as a study, it became apparent that these data could be of interest as an indicator for national dietary trends. Food intake was reported (by weighing or estimating the amounts) for two weekdays and one weekend day per student, along with age, length, sex and weight. Food intake was translated to nutrient intake using Dietist Net software (Kost & Näringsdata).  Admittedly, the data set has some validity problems: the students differ from the Riksmaten study groups in mean age and geographical distribution, and all data was collected during March-April. As students in a nutrition course, they can also be expected to be more interested and more knowledgeable in the nutrition subject than the average person. Nevertheless, the results clearly demonstrate a substantial change in nutrient intake from 2006 and onwards, where the energy from carbohydrates decreased from above 50% to below 40%, and where the energy intake from fat increased from about 25% to 36%. Further details, such as the effects on the intake of selected micronutrients, will be presented.

Series
Food & Nutrition Research, ISSN 1654-661X ; 60:31961
National Category
Nutrition and Dietetics
Research subject
Natural Science, Medicine
Identifiers
urn:nbn:se:lnu:diva-56303 (URN)
Conference
11th Nordic Nutrition Conference, June 20-22, Gothenburg
Available from: 2016-09-02 Created: 2016-09-02 Last updated: 2018-11-02Bibliographically approved
Duong-Thi, M.-D., Bergström, M., Edwards, K., Eriksson, J., Ohlson, S., To Yiu Ying, J., . . . Agmo Hernández, V. (2016). Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins. The Analyst, 141(3), 981-988
Open this publication in new window or tab >>Lipodisks integrated with weak affinity chromatography enable fragment screening of integral membrane proteins
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2016 (English)In: The Analyst, ISSN 0003-2654, E-ISSN 1364-5528, Vol. 141, no 3, p. 981-988Article in journal (Refereed) Published
Abstract [en]

Membrane proteins constitute the largest class of drug targets but they present many challenges in drug discovery. Importantly, the discovery of potential drug candidates is hampered by the limited availability of efficient methods for screening drug-protein interactions. In this work we present a novel strategy for rapid identification of molecules capable of binding to a selected membrane protein. An integral membrane protein (human aquaporin-1) was incorporated into planar lipid bilayer disks (lipodisks), which were subsequently covalently coupled to porous derivatized silica and packed into HPLC columns. The obtained affinity columns were used in a typical protocol for fragment screening by weak affinity chromatography (WAC), in which one hit was identified out of a 200 compound collection. The lipodisk-based strategy, which ensures a stable and native-like lipid environment for the protein, is expected to work also with other membrane proteins and screening procedures.

National Category
Analytical Chemistry
Research subject
Chemistry, Analytical Chemistry
Identifiers
urn:nbn:se:lnu:diva-50634 (URN)10.1039/c5an02105g (DOI)000368942600028 ()26673836 (PubMedID)2-s2.0-84956759926 (Scopus ID)
Available from: 2016-03-11 Created: 2016-03-11 Last updated: 2017-11-30Bibliographically approved
Duong-Thi, M.-D., Bergström, G., Mandenius, C.-F., Bergström, M., Fex, T. & Ohlson, S. (2014). Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules. Analytical Biochemistry, 461, 57-59
Open this publication in new window or tab >>Comparison of weak affinity chromatography and surface plasmon resonance in determining affinity of small molecules
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2014 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 461, p. 57-59Article in journal (Refereed) Published
Abstract [en]

In this study, we compared affinity data from surface plasmon resonance (SPR) and weak affinity chromatography (WAC), two established techniques for determination of weak affinity (mM-mu M) small molecule-protein interactions. In the current comparison, thrombin was used as target protein. In WAC the affinity constant (K-D) was determined from retention times, and in SPR it was determined by Langmuir isotherm fitting of steady-state responses. Results indicate a strong correlation between the two methods (R-2 = 0.995, P < 0.0001). (C) 2014 Elsevier Inc. All rights reserved.

Keywords
Affinity determination, Fragment-based drug discovery, Surface plasmon resonance, Thrombin, Weak affinity chromatography
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-36862 (URN)10.1016/j.ab.2014.05.023 (DOI)000340077600009 ()2-s2.0-84903973479 (Scopus ID)
Available from: 2014-09-10 Created: 2014-09-10 Last updated: 2017-12-05Bibliographically approved
Duong-Thi, M.-D., Bergström, M., Fex, T., Isaksson, R. & Ohlson, S. (2013). High-Throughput Fragment Screening by Affinity LC-MS. Journal of Biomolecular Screening, 18(2), 160-171
Open this publication in new window or tab >>High-Throughput Fragment Screening by Affinity LC-MS
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2013 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 18, no 2, p. 160-171Article in journal (Refereed) Published
Abstract [en]

Fragment screening, an emerging approach for hit finding in drug discovery, has recently been proven effective by its first approved drug, vemurafenib, for cancer treatment. Techniques such as nuclear magnetic resonance, surface plasmon resonance, and isothemal titration calorimetry, with their own pros and cons, have been employed for screening fragment libraries. As an alternative approach, screening based on high-performance liquid chromatography separation has been developed. In this work, we present weak affinity LC/MS as a method to screen fragments under high-throughput conditions. Affinity-based capillary columns with immobilized thrombin were used to screen a collection of 590 compounds from a fragment library. The collection was divided into 11 mixtures (each containing 35 to 65 fragments) and screened by MS detection. The primary screening was performed in < 4 h (corresponding to > 3500 fragments per day). Thirty hits were defined, which subsequently entered a secondary screening using an active site-blocked thrombin column for confirmation of specificity. One hit showed selective binding to thrombin with an estimated dissociation constant (K-D) in the 0.1 mM range. This study shows that affinity LC/MS is characterized by high throughput, ease of operation, and low consumption of target and fragments, and therefore it promises to be a valuable method for fragment screening.

Keywords
drug discovery, fragment screening, mass spectrometry, thrombin, weak affinity chromatography
National Category
Biochemistry and Molecular Biology
Research subject
Chemistry, Biochemistry; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-24535 (URN)10.1177/1087057112459271 (DOI)000313661900002 ()2-s2.0-84872546422 (Scopus ID)
Available from: 2013-02-25 Created: 2013-02-25 Last updated: 2017-12-06Bibliographically approved
Duong-Thi, M.-D., Bergström, M., Fex, T., Svensson, S., Ohlson, S. & Isaksson, R. (2013). Weak Affinity Chromatography for Evaluation of Stereoisomers in Early Drug Discovery. Journal of Biomolecular Screening, 18(6), 748-755
Open this publication in new window or tab >>Weak Affinity Chromatography for Evaluation of Stereoisomers in Early Drug Discovery
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2013 (English)In: Journal of Biomolecular Screening, ISSN 1087-0571, E-ISSN 1552-454X, Vol. 18, no 6, p. 748-755Article in journal (Refereed) Published
Abstract [en]

In early drug discovery (e.g. in fragment screening), recognition of stereoisomeric structures is valuable and guides medicinal chemists to focus only on useful configurations. In this work, we concurrently screened mixtures of stereoisomers and estimated their affinities to a protein target (thrombin) using weak affinity chromatography-mass spectrometry (WAC-MS). Affinity determinations by WAC showed that minor changes in stereoisomeric configuration could have major impact on affinity. The ability of WAC-MS to provide instant information about stereoselectivity and binding affinities directly from analyte mixtures is a great advantage in fragment library screening and drug lead development.

Place, publisher, year, edition, pages
Sage Publications, 2013
Keywords
fragment-based drug discovery, mixture screening, stereoisomers, thrombin, weak affinity chromatography
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Natural Science, Biomedical Sciences; Chemistry, Biochemistry
Identifiers
urn:nbn:se:lnu:diva-24641 (URN)10.1177/1087057113480391 (DOI)000320888100013 ()2-s2.0-84879476954 (Scopus ID)
Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2019-06-25Bibliographically approved
Landström, J., Bergström, M., Hamark, C., Ohlson, S. & Widmalm, G. (2012). Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies.. Organic and biomolecular chemistry, 10(15), 3019-3032
Open this publication in new window or tab >>Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies.
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2012 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, no 15, p. 3019-3032Article in journal (Refereed) Published
Abstract [en]

By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using (1)H saturation transfer difference (STD) effects and transferred (1)H,(1)H-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides β-d-Galp-(1→4)-β-D-GlcpNAc-OMe and β-D-GlcpNAc-(1→4)-β-D-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/π-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N'-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on (1)H NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process.

National Category
Chemical Sciences
Research subject
Natural Science
Identifiers
urn:nbn:se:lnu:diva-18565 (URN)10.1039/c2ob07066a (DOI)22395160 (PubMedID)2-s2.0-84858969506 (Scopus ID)
Available from: 2012-05-05 Created: 2012-05-05 Last updated: 2017-12-07Bibliographically approved
Bergström, M., Åström, E., Påhlsson, P. & Ohlson, S. (2012). Elucidating the selectivity of recombinant forms of Aleuria aurantia lectin using weak affinity chromatography. Journal of chromatography. B, 885-886, 66-72
Open this publication in new window or tab >>Elucidating the selectivity of recombinant forms of Aleuria aurantia lectin using weak affinity chromatography
2012 (English)In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 885-886, p. 66-72Article in journal (Refereed) Published
Abstract [en]

Aberrant glycosylation is connected to several pathological conditions and lectins are useful tools to characterize glycosylated biomarkers. The Aleuria aurantia lectin (AAL) is of special interest since it interacts with all types of fucosylated saccharides. AAL has been expressed in E.coli as a fully functional recombinant protein. Engineered variants of AAL have been developed with the aim of creating monovalent lectins with more homogenous binding characteristics. Four different forms of AAL were studied in the present work: native AAL purified from Aleuria aurantia mushrooms, recombinant AAL dimer, recombinant AAL monomer and recombinant AAL site 2 (S2-AAL). The affinities of these AAL forms towards a number of saccharides were determined with weak affinity chromatography (WAC). Disaccharides with fucose linked α1-3 to GlcNAc interacted with higher affinity compared to fucose linked α1-6 or α1-4 and the obtained dissociation constants (Kd) were in the range of 10 μM for all AAL forms. Tetra- and pentasaccharides with fucose in α1-2, α1-3 or α1-4 had Kd values ranging from 0.1–7 mM while a large α1-6 fucosylated oligosaccharide had a Kd of about 20 μM. The recombinant multivalent AAL forms and native AAL exhibited similar affinities towards all saccharides, but S2-AAL had a lower affinity especially regarding a sialic acid containing fucosylated saccharide. It was demonstrated that WAC is a valuable technique in determining the detailed binding profile of the lectins. Specific advantages with WAC include a low consumption of non-labeled saccharides, possibility to analyze mixtures and a simple procedure using standard HPLC equipment.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Affinity; Aleuria aurantia lectin; Glycan interaction; Recombinant protein; Weak Affinity Chromatography
National Category
Chemical Sciences
Research subject
Chemistry, Biotechnology
Identifiers
urn:nbn:se:lnu:diva-16303 (URN)10.1016/j.jchromb.2011.12.015 (DOI)2-s2.0-84856642608 (Scopus ID)
Available from: 2012-05-04 Created: 2011-12-22 Last updated: 2017-12-08Bibliographically approved
Duong-Thi, M.-D., Meiby, E., Bergström, M., Fex, T., Isaksson, R. & Ohlson, S. (2011). Weak affinity chromatography as a new approach for fragment screening in drug discovery. Analytical Biochemistry, 414(1), 138-146
Open this publication in new window or tab >>Weak affinity chromatography as a new approach for fragment screening in drug discovery
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2011 (English)In: Analytical Biochemistry, ISSN 0003-2697, E-ISSN 1096-0309, Vol. 414, no 1, p. 138-146Article in journal (Refereed) Published
Abstract [en]

Fragment-based drug design (FBDD) is currently being implemented in drug discovery, creating a demand for developing efficient techniques for fragment screening. Due to the intrinsic weak or transient binding of fragments (mM–uM in dissociation constant (KD)) to targets, methods must be sensitive enough to accurately detect and quantify an interaction. This study presents weak affinity chromatography (WAC) as an alternative tool for screening of small fragments. The technology was demonstrated by screening of a selected 23 compound fragment collection of documented binders, mostly amidines, using trypsin and thrombin as model target protease proteins. WAC was proven to be a sensitive, robust, and reproducible technique that also provides information about affinity of a fragment in the range of 1 mM–10uM. Furthermore, it has potential for high throughput as was evidenced by analyzing mixtures in the range of 10 substances by WAC–MS. The accessibility and flexibility of the technology were shown as fragment screening can be performed on standard HPLC equipment. The technology can further be miniaturized and adapted to the requirements of affinity ranges of the fragment library. All these features of WAC make it a potential method in drug discovery for fragment screening.

Place, publisher, year, edition, pages
Elsevier, 2011
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Analytical Chemistry
Research subject
Natural Science, Biochemistry; Natural Science, Biomedical Sciences
Identifiers
urn:nbn:se:lnu:diva-24639 (URN)10.1016/j.ab.2011.02.022 (DOI)2-s2.0-79955686355 (Scopus ID)
Available from: 2013-03-01 Created: 2013-03-01 Last updated: 2017-12-06Bibliographically approved
Cheshev, P., Morelli, L., Marchesi, M., Podlipnik, C., Bergström, M. & Bernardi, A. (2010). Synthesis and affinity evaluation of a small library of bidentate cholera toxin ligands: towards nonhydrolyzable ganglioside mimics. Chemistry - A European Journal, 16(6), 1951-1967
Open this publication in new window or tab >>Synthesis and affinity evaluation of a small library of bidentate cholera toxin ligands: towards nonhydrolyzable ganglioside mimics
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2010 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 16, no 6, p. 1951-1967Article in journal (Refereed) Published
Abstract [en]

A small library of nonhydrolyzable mimics of GM1 ganglioside, featuring galactose and sialic acid its pharmacophoric carbohydrate residues,, was synthesized and tested. All compounds were synthesized from readily available precursors using high-performance reactions, including click chemistry protocols, and avoiding O-glycosidic bonds. Sonic of the most active molecules also feature a point of further derivatization that can be used for conjugation will, polyvalent aglycons. Their affinity towards cholera toxin was assessed by weak affinity chromatography, which allowed a systematic evaluation and selection of the best candidates. Affinity could be enhanced up to one or two orders of magnitude over the affinity of the individual pharmacophoric sugar residues.

National Category
Organic Chemistry
Research subject
Natural Science, Biotechnology; Natural Science; Natural Science, Biochemistry; Natural Science, Organic Chemistry
Identifiers
urn:nbn:se:lnu:diva-2034 (URN)10.1002/chem.200902469 (DOI)
Available from: 2010-04-06 Created: 2010-04-06 Last updated: 2017-12-12Bibliographically approved
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