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Publications (10 of 34) Show all publications
Mesas-Sanchez, L., Diaz-Alvarez, A. E., Koukal, P. & Diner, P. (2014). Kinetic resolution of 2-hydroxy-2-aryl-ethylphosphonates by a non-enzymatic acylation catalyst. Tetrahedron, 70(24), 3807-3811
Open this publication in new window or tab >>Kinetic resolution of 2-hydroxy-2-aryl-ethylphosphonates by a non-enzymatic acylation catalyst
2014 (English)In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 70, no 24, p. 3807-3811Article in journal (Refereed) Published
Abstract [en]

Optically pure hydroxyphosphonates are widely used as derivatizable compounds that can be incorporated into a variety of synthetic strategies for the preparation of other high value organic products. A non-enzymatic kinetic resolution procedure to obtain chiral 2-hydroxy-2-arylethylphosphonates from the easily available racemic counterparts is described. A range of 2-hydroxy-2-arylethylphosphonates was efficiently resolved employing a planar-chiral DMAP derived catalyst with good selectivities (up to S=68). The chiral hydroxyphosphonates were isolated in good yields and high enantiomeric excess (>94% ee).

Keyword
Non-enzymatic kinetic resolution, 2-Hydroxy-2-arylethylphosphonates, Planar chiral DMAP derivative catalyst
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-227994 (URN)10.1016/j.tet.2014.03.102 (DOI)000336710200010 ()
Available from: 2014-07-04 Created: 2014-07-02 Last updated: 2017-12-05Bibliographically approved
Poon, J.-F., Alao, J. P., Sunnerhagen, P. & Dinér, P. (2013). Azastilbenes: a cut-off to p38 MAPK inhibitors. Organic and biomolecular chemistry, 11(27), 4526-4536
Open this publication in new window or tab >>Azastilbenes: a cut-off to p38 MAPK inhibitors
2013 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 11, no 27, p. 4526-4536Article in journal (Refereed) Published
Abstract [en]

Inhibitors with vicinal 4-fluorophenyl/4-pyridine rings on a five- or six-membered heterocyclic ring are known to inhibit the p38 mitogen-activated protein kinase (MAPK), which is a potential target for rheumatoid arthritis and several different types of cancer. Several substituted azastilbene-based compounds with vicinal 4-fluorophenyl/4-pyridine rings were designed using computational docking, synthesized, and evaluated in a cell-free radiometric p38[small alpha] assay. The biochemical evaluation shows that the best inhibition (down to 110 nM) is achieved for azastilbene-based compounds having an isopropylamine substituent in the 2-position of the pyridine ring. The inhibition of p38 signaling in human breast cancer cells was observed for two of the compounds.

National Category
Organic Chemistry
Research subject
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-201387 (URN)10.1039/C3OB27449G (DOI)000321601000015 ()
Available from: 2013-06-10 Created: 2013-06-10 Last updated: 2017-12-06Bibliographically approved
Amorati, R., Valgimigli, L., Dinér, P., Bakhtiari, K., Saeedi, M. & Engman, L. (2013). Multi-faceted reactivity of alkyltellurophenols towards peroxyl radicals: Catalytic antioxidant versus thiol-depletion effect. Chemistry - A European Journal, 19(23), 7510-7522
Open this publication in new window or tab >>Multi-faceted reactivity of alkyltellurophenols towards peroxyl radicals: Catalytic antioxidant versus thiol-depletion effect
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2013 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 23, p. 7510-7522Article in journal (Refereed) Published
Abstract [en]

Hydroxyaryl alkyl tellurides are effective antioxidants both in organic solution and aqueous biphasic systems. They react by an unconventional mechanism with ROO. radicals with rate constants as high as 107M1s1 at 303K, outperforming common phenols. The reactions proceed by oxygen atom transfer to tellurium followed by hydrogen atom transfer to the resulting RO. radical from the phenolic OH. The reaction rates do not reflect the electronic properties of the ring substituents and, because the reactions occur in a solvent cage, quenching is more efficient when the OH and TeR groups have an ortho arrangement. In the presence of thiols, hydroxyaryl alkyl tellurides act as catalytic antioxidants towards both hydroperoxides (mimicking the glutathione peroxidases) and peroxyl radicals. The high efficiency of the quenching of the peroxyl radicals and hydroperoxides could be advantageous under normal cellular conditions, but pro-oxidative (thiol depletion) when thiol concentrations are low.

Keyword
antioxidants, kinetics, pro-oxidants, radicals, tellurium
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-201892 (URN)10.1002/chem.201300451 (DOI)000319417500028 ()
Available from: 2013-06-17 Created: 2013-06-17 Last updated: 2017-12-06Bibliographically approved
Díaz-Álvarez, A. E., Mesas-Sánchez, L. & Dinér, P. (2013). Nichtenzymatische dynamische kinetische Racematspaltung sekundärer Arylalkohole: planar-chirale Ferrocen- und Rutheniumkatalysatoren im Zusammenspiel. Angewandte Chemie, 125(2), 522-524
Open this publication in new window or tab >>Nichtenzymatische dynamische kinetische Racematspaltung sekundärer Arylalkohole: planar-chirale Ferrocen- und Rutheniumkatalysatoren im Zusammenspiel
2013 (English)In: Angewandte Chemie, ISSN 1521-3757, Vol. 125, no 2, p. 522-524Article in journal (Refereed) Published
Keyword
Acylierungen, Chiralität, Kinetische Racematspaltung, Sekundäre Alkohole
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-189455 (URN)10.1002/ange.201207648 (DOI)
Available from: 2013-01-02 Created: 2013-01-02 Last updated: 2013-08-20Bibliographically approved
Díaz-Álvarez, A. E., Mesas Sanchez, L. & Dinér, P. (2013). Non-Enzymatic Dynamic Kinetic Resolution of Secondary Aryl Alcohols: Planar Chiral Ferrocene and Ruthenium Catalysts in Cooperation. Angewandte Chemie International Edition, 52(2), 502-504
Open this publication in new window or tab >>Non-Enzymatic Dynamic Kinetic Resolution of Secondary Aryl Alcohols: Planar Chiral Ferrocene and Ruthenium Catalysts in Cooperation
2013 (English)In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 2, p. 502-504Article in journal (Refereed) Published
Keyword
acylation, chiral resolution, kinetic resolution, secondary alcohols
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-189453 (URN)10.1002/anie.201207648 (DOI)000312942900002 ()
Available from: 2013-01-02 Created: 2013-01-02 Last updated: 2017-12-06Bibliographically approved
Mesas-Sánchez, L., Díaz-Álvarez, A. E. & Dinér, P. (2013). Non-enzymatic kinetic resolution of 1,2-azidoalcohols using a planar-chiral DMAP derivative catalyst. Tetrahedron, 69(2), 753-757
Open this publication in new window or tab >>Non-enzymatic kinetic resolution of 1,2-azidoalcohols using a planar-chiral DMAP derivative catalyst
2013 (English)In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 69, no 2, p. 753-757Article in journal (Refereed) Published
Abstract [en]

Optically pure 1,2-azidoalcohols are widely used as precursors for other high value organic products. A non-enzymatic kinetic resolution procedure for the stereoselective synthesis of chiral 1,2-azidoalcohols from the readily available racemic counterparts has been developed, employing a planar-chiral DMAP derivative catalyst. Following this procedure, a range of aromatic 1,2-azidoalcohols was obtained in good selectivities (up to S=45) and high enantiomeric excess (up to 99% ee).

Keyword
Non-enzymatic kinetic resolution, 1, 2-Azidoalcohols, Planar-chiral DMAP derivative catalyst, Ferrocenyl catalyst
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-189450 (URN)10.1016/j.tet.2012.10.077 (DOI)000314371800045 ()
Available from: 2013-01-02 Created: 2013-01-02 Last updated: 2017-12-06Bibliographically approved
Hamngren, C., Dinér, P., Grøtli, M., Goksör, M. & Adiels, C. B. (2012). Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling. In: Proceedings of SPIE: The International Society for Optical Engineering. Paper presented at Optical Trapping and Optical Micromanipulation IX, 12 August 2012 through 16 August 2012, San Diego, CA (pp. 84582K).
Open this publication in new window or tab >>Design and evaluation of a microfluidic system for inhibition studies of yeast cell signaling
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2012 (English)In: Proceedings of SPIE: The International Society for Optical Engineering, 2012, p. 84582K-Conference paper, Published paper (Refereed)
Abstract [en]

In cell signaling, different perturbations lead to different responses and using traditional biological techniques that result in averaged data may obscure important cell-to-cell variations. The aim of this study was to develop and evaluate a four-inlet microfluidic system that enables single-cell analysis by investigating the effect on Hog1 localization post a selective Hog1 inhibitor treatment during osmotic stress. Optical tweezers was used to position yeast cells in an array of desired size and density inside the microfluidic system. By changing the flow rates through the inlet channels, controlled and rapid introduction of two different perturbations over the cell array was enabled. The placement of the cells was determined by diffusion rates flow simulations. The system was evaluated by monitoring the subcellular localization of a fluorescently tagged kinase of the yeast "High Osmolarity Glycerol" (HOG) pathway, Hog1-GFP. By sequential treatment of the yeast cells with a selective Hog1 kinase inhibitor and sorbitol, the subcellular localization of Hog1-GFP was analysed on a single-cell level. The results showed impaired Hog1-GFP nuclear localization, providing evidence of a congenial design. The setup made it possible to remove and add an agent within 2 seconds, which is valuable for investigating the dynamic signal transduction pathways and cannot be done using traditional methods. We are confident that the features of the four-inlet microfluidic system will be a valuable tool and hence contribute significantly to unravel the mechanisms of the HOG pathway and similar dynamic signal transduction pathways.

Series
Proceedings of SPIE - The International Society for Optical Engineering, ISSN 0277-786X ; 8458
Keyword
Microfluidics, Optical manipulation, Signal transduction pathways, Single-cell analysis, Biological techniques, Cell array, Cell signaling, Cell-to-cell variation, Diffusion rate, Dynamic signals, HOG pathway, Inlet channels, Kinase inhibitors, Micro fluidic system, Nuclear localization, Osmolarity, Osmotic stress, Sequential treatments, Single-cell level, Singlecell analysis, Subcellular localizations, Yeast cell, Cells, Cytology, Fluidic devices, Glycerol, Micromanipulators, Optical tweezers, Signal transduction, Yeast, Molecular biology
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-195457 (URN)10.1117/12.929728 (DOI)978-081949175-6 (ISBN)
Conference
Optical Trapping and Optical Micromanipulation IX, 12 August 2012 through 16 August 2012, San Diego, CA
Available from: 2013-02-26 Created: 2013-02-25 Last updated: 2013-02-26Bibliographically approved
Dinér, P., Alao, J. P., Söderlund, J., Sunnerhagen, P. & Grøtli, M. (2012). Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET Kinase Inhibitors. Journal of Medicinal Chemistry, 55(10), 4872-4876
Open this publication in new window or tab >>Preparation of 3-Substituted-1-Isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines as RET Kinase Inhibitors
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2012 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 55, no 10, p. 4872-4876Article in journal (Refereed) Published
Abstract [en]

A series of 3-substituted-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amines have been designed, synthesized, and evaluated as RET protein kinase inhibitors. On the basis of docking results, a small library of pyrazolopyrimidine compounds with an extended hydrophobic side arm was synthesized. The most promising of the compounds (7a) displayed efficient inhibition in vitro and good selectivity when tested on a panel of kinases. Furthermore, 7a inhibited GDNF-induced RET phosphorylation of ERK1/2 in MCF-7 breast cancer cells at concentrations as low as 100 nM.

National Category
Natural Sciences
Research subject
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-174622 (URN)10.1021/jm3003944 (DOI)
Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
Dinér, P. (2012). Superacid-Promoted Ionization of Alkanes Without Carbonium Ion Formation: A Density Functional Theory Study. Journal of Physical Chemistry A, 116(40), 9979-9984
Open this publication in new window or tab >>Superacid-Promoted Ionization of Alkanes Without Carbonium Ion Formation: A Density Functional Theory Study
2012 (English)In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 116, no 40, p. 9979-9984Article in journal (Refereed) Published
Abstract [en]

The carbonium ion has been suggested to be the intermediate in superacid-promoted reactions (SbF5-HF) such as hydrogen-deuterium exchange and in the electrophilic C-H cleavage into hydrogen and the carbenium ion. In this study, the superacid-promoted C-H cleavage into hydrogen and the carbenium ion was studied using density functional theory (B3LYP and M062X) and ab initio methods (MP2 and CCSD). The calculations suggest that the superacid-promoted C-H cleavage proceeds via a concerted transition state leading to hydrogen (H-2) and the carbenium ion without the formation of the elusive carbonium ion. The reactivity for the superacid promoted C-H cleavage decreases upon going from isobutane (tertiary) > propane (secondary) > isobutane (primary) > propane (primary) > ethane >> methane.

National Category
Organic Chemistry Theoretical Chemistry
Identifiers
urn:nbn:se:uu:diva-181675 (URN)10.1021/jp306319s (DOI)000309648800023 ()
Available from: 2012-09-27 Created: 2012-09-27 Last updated: 2017-12-07Bibliographically approved
Dierckx, A., Dinér, P., El-Sagheer, A. H., Kumar, J. D., Brown, T., Grøtli, M. & Wilhelmsson, L. M. (2011). Characterization of photophysical and base-mimicking properties of a novel fluorescent adenine analogue in DNA.. Nucleic Acids Research, 39(10), 4513-24
Open this publication in new window or tab >>Characterization of photophysical and base-mimicking properties of a novel fluorescent adenine analogue in DNA.
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2011 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 39, no 10, p. 4513-24Article in journal (Refereed) Published
Abstract [en]

To increase the diversity of fluorescent base analogues with improved properties, we here present the straightforward click-chemistry-based synthesis of a novel fluorescent adenine-analogue triazole adenine (A(T)) and its photophysical characterization inside DNA. A(T) shows promising properties compared to the widely used adenine analogue 2-aminopurine. Quantum yields reach >20% and >5% in single- and double-stranded DNA, respectively, and show dependence on neighbouring bases. Moreover, A(T) shows only a minor destabilization of DNA duplexes, comparable to 2-aminopurine, and circular dichroism investigations suggest that A(T) only causes minimal structural perturbations to normal B-DNA. Furthermore, we find that A(T) shows favourable base-pairing properties with thymine and more surprisingly also with normal adenine. In conclusion, A(T) shows strong potential as a new fluorescent adenine analogue for monitoring changes within its microenvironment in DNA.

Identifiers
urn:nbn:se:uu:diva-154406 (URN)10.1093/nar/gkr010 (DOI)21278417 (PubMedID)
Available from: 2011-06-01 Created: 2011-06-01 Last updated: 2017-12-11
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-6782-6622

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