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  1. Article ; Online: Young Investigator Interview With CSCI Distinguished Scientist Awardee Dr. Michael Hill.

    Wang, Wenxuan / Hill, Michael D

    Clinical and investigative medicine. Medecine clinique et experimentale

    2022  Volume 45, Issue 1, Page(s) E9–11

    Abstract: Dr. Michael Hill is President of the Canadian Neurology Federation and Director of the Stroke Unit ... Neurosciences. Dr. Hill has made outstanding contributions to the field of stroke research, particularly ... through the ESCAPE and ESCAPE-NA1 trials. Dr. Hill was a recipient of the Canadian Society for Clinical Investigation ...

    Abstract Dr. Michael Hill is President of the Canadian Neurology Federation and Director of the Stroke Unit for the Calgary Stroke Program. He is also a professor at the University of Calgary at the Department of Clinical Neurosciences. Dr. Hill has made outstanding contributions to the field of stroke research, particularly through the ESCAPE and ESCAPE-NA1 trials. Dr. Hill was a recipient of the Canadian Society for Clinical Investigation (CSCI) Distinguished Scientist Award in 2021-recognized as an expert and innovative leader in his research.
    MeSH term(s) Biomedical Research ; Canada ; Humans ; Physicians ; Research Personnel ; Stroke
    Language English
    Publishing date 2022-03-23
    Publishing country Canada
    Document type Interview
    ZDB-ID 434004-8
    ISSN 1488-2353 ; 0147-958X
    ISSN (online) 1488-2353
    ISSN 0147-958X
    DOI 10.25011/cim.v45i1.38099
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1389: Show issues Location:
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    Zs.MO 345: Show issues

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  2. Article: Isolation and Characterization of Antibodies: the Work of Michael Sela

    Kresge, Nicole / Simoni, Robert D / Hill, Robert L

    Journal of biological chemistry. 2010 Sept. 24, v. 285, no. 39

    2010  

    Language English
    Dates of publication 2010-0924
    Size p. e12-e14.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Rational design of resorcylic acid lactone analogues as covalent MNK1/2 kinase inhibitors by tuning the reactivity of an enamide Michael acceptor.

    Xu, Jin / Chen, Anqi / Joy, Joma / Xavier, Vanessa Joanne / Ong, Esther H Q / Hill, Jeffrey / Chai, Christina L L

    ChemMedChem

    2013  Volume 8, Issue 9, Page(s) 1483–1494

    Abstract: Recent biological and computational advances in drug design have led to renewed interest in targeted covalent inhibition as an efficient and practical approach for the development of new drugs. As part of our continuing efforts in the exploration of the ... ...

    Abstract Recent biological and computational advances in drug design have led to renewed interest in targeted covalent inhibition as an efficient and practical approach for the development of new drugs. As part of our continuing efforts in the exploration of the therapeutic potential of resorcylic acid lactones (RALs), we report herein the design, synthesis, and biological evaluation of conveniently accessible RAL enamide analogues as novel covalent inhibitors of MAP kinase interacting kinases (MNKs). In this study, we have successfully demonstrated that the covalent binding ability of RAL enamides can be tuned by attaching an electron-withdrawing motif, such as an acyl group, to enhance its reactivity toward the cysteine residues at the MNK1/2 binding sites. We have also shown that ¹H NMR spectroscopy is a convenient and effective tool for screening the covalent binding activities of enamides using cysteamine as a mimic of the key cysteine residue in the enzyme, whereas mass spectrometric analysis confirms covalent modification of the kinases. Preliminary optimization of the initial hit led to the discovery of enamides with low micromolar activity in MNK assays. Cancer cell line assays have identified RAL enamides that inhibit the growth of cancer cells with similar potency to the natural product L-783,277.
    MeSH term(s) Amides/chemical synthesis ; Amides/chemistry ; Amides/toxicity ; Cell Line, Tumor ; Cell Survival/drug effects ; Crystallography, X-Ray ; Drug Design ; HeLa Cells ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors ; Intracellular Signaling Peptides and Proteins/metabolism ; Isomerism ; Kinetics ; Lactones/chemical synthesis ; Lactones/chemistry ; Lactones/toxicity ; Protein Binding ; Protein Kinase Inhibitors/chemical synthesis ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/toxicity ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Protein-Serine-Threonine Kinases/metabolism ; Resorcinols/chemistry ; Resorcinols/toxicity
    Chemical Substances Amides ; Intracellular Signaling Peptides and Proteins ; L 783277 ; Lactones ; Protein Kinase Inhibitors ; Resorcinols ; MKNK1 protein, human (EC 2.7.1.-) ; MKNK2 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2013-09
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2218496-X
    ISSN 1860-7187 ; 1860-7179
    ISSN (online) 1860-7187
    ISSN 1860-7179
    DOI 10.1002/cmdc.201300231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6280: Show issues Location:
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  4. Article ; Online: Mechanistic insights into the Michael addition of deoxyguanosine to catechol estrogen-3,4-quinones.

    Stack, Douglas E / Li, Guangping / Hill, Anastacia / Hoffman, Nicholas

    Chemical research in toxicology

    2008  Volume 21, Issue 7, Page(s) 1415–1425

    Abstract: ... as a result of Michael addition of deoxyguanosine (dG) to catechol estrogen-3,4-quninones, have been modeled ... that a proton source is needed to effect the Michael addition. Calculations also indicate that a catalytic ... results are consistent with a mechanism that involves a proton-assisted Michael addition to form an alpha ...

    Abstract The reaction of catechol estrogen quinones with DNA to produce the depurinating adducts, 4-OHE 2(E 1)-1-N7Gua and 4-OHE 2(E 1)-1-N3Ade, has been linked to the initiation of breast and other human cancers. A better understanding into the mechanism of how these adducts are formed would be useful to studies aimed at correlating adduct formation to DNA damage. Possible reaction intermediates, produced as a result of Michael addition of deoxyguanosine (dG) to catechol estrogen-3,4-quninones, have been modeled using density functional theory to determine likely intermediates on the potential energy surface (PES) of this reaction. Specifically, the sequence of elimination events, glycosidic bond cleavage and rearomatization of the estrogen A ring, was explored. Consistent with known experimental procedures, B3LYP calculations indicate that a proton source is needed to effect the Michael addition. Calculations also indicate that a catalytic mechanism, where one catechol estrogen quinone could adduct multiple purine bases, is unlikely. Experimental investigation toward an observed cationic reaction intermediate was also consistent with a stoichiometric reaction between estrone-3,4-quinone (E 1-3,4-Q) and dG. HPLC-MS analysis indicates that the cationic reaction intermediate contains the 2'-deoxyribose moiety. Assay of 4-OHE 1-1-N7Gua adduct formation and 2'-deoxyribose formation at different times during the reaction of E 1-3,4-Q with dG indicates that equimolar amounts of each are produced, further supporting a stoichiometric process with respect the catechol estrogen quinone. Differences in the UV spectroscopy of cationic reaction intermediate and the 4-OHE 1-1-N7Gua adduct allowed for kinetic analysis of the glycosidic bond cleavage process. Kinetic scanning analysis indicates that the decomposition of the cationic reaction intermediate is a first-order process with a t 1/2 of 40 min at 30 degrees C. Measurement of the unimolecular rate constant k at different temperatures afforded an Arrhenius plot, which provided values for Delta H, Delta S, and Delta G of 24.7 kcal/mol, 7.2 eu, and 26.8 kcal/mol, respectively. The computational data in conjunction with experimental results are consistent with a mechanism that involves a proton-assisted Michael addition to form an alpha-ketoenol ring system, followed by slow loss of the proton at C1 to restore the aromatic A ring, then fast cleavage of the glycosidic bond to form the 4-OHE 1-1-N7Gua adduct.
    MeSH term(s) Carcinogens/chemistry ; Carcinogens/metabolism ; Chromatography, High Pressure Liquid ; DNA Adducts/chemistry ; DNA Adducts/metabolism ; DNA Damage ; Deoxyguanosine/chemistry ; Deoxyguanosine/metabolism ; Estradiol/analogs & derivatives ; Estradiol/chemistry ; Estradiol/metabolism ; Mass Spectrometry ; Thermodynamics
    Chemical Substances Carcinogens ; DNA Adducts ; hexestrol-3',4'-quinone ; Estradiol (4TI98Z838E) ; Deoxyguanosine (G9481N71RO)
    Language English
    Publishing date 2008-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 639353-6
    ISSN 1520-5010 ; 0893-228X
    ISSN (online) 1520-5010
    ISSN 0893-228X
    DOI 10.1021/tx800071u
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2320: Show issues Location:
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  5. Article ; Online: Automated synthesis of a library of triazolated 1,2,5-thiadiazepane 1,1-dioxides via a double aza-Michael strategy.

    Zang, Qin / Javed, Salim / Hill, David / Ullah, Farman / Bi, Danse / Porubsky, Patrick / Neuenswander, Benjamin / Lushington, Gerald H / Santini, Conrad / Organ, Michael G / Hanson, Paul R

    ACS combinatorial science

    2012  Volume 14, Issue 8, Page(s) 456–459

    Abstract: ... double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized ...

    Abstract The construction of a 96-member library of triazolated 1,2,5-thiadiazepane 1,1-dioxides was performed on a Chemspeed Accelerator (SLT-100) automated parallel synthesis platform, culminating in the successful preparation of 94 out of 96 possible products. The key step, a one-pot, sequential elimination, double-aza-Michael reaction, and [3 + 2] Huisgen cycloaddition pathway has been automated and utilized in the production of two sets of triazolated sultam products.
    MeSH term(s) Automation ; Aza Compounds/chemistry ; Azepines/chemical synthesis ; Azepines/chemistry ; Combinatorial Chemistry Techniques ; Molecular Structure ; Small Molecule Libraries/chemical synthesis ; Small Molecule Libraries/chemistry ; Sulfur/chemistry
    Chemical Substances 1,4-diazepane ; Aza Compounds ; Azepines ; Small Molecule Libraries ; Sulfur (70FD1KFU70)
    Language English
    Publishing date 2012-08-01
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2156-8944
    ISSN (online) 2156-8944
    DOI 10.1021/co300049u
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: The Development of Site-directed Mutagenesis by Michael Smith

    Kresge, Nicole / Simoni, Robert D / Hill, Robert L

    Journal of biological chemistry. 2006 Sept. 29, v. 281, no. 39

    2006  

    Language English
    Dates of publication 2006-0929
    Size p. e31.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 4' 65/118: Show issues
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  7. Book ; Conference proceedings: Jakob Michael Reinhold Lenz

    Hill, David

    Studien zum Gesamtwerk ; [... Beiträge zu einem internationalen Symposium, das aus Anlaß des 200. Todestages von Jakob Michael Reinhold Lenz im September 1992 in Birmingham, England, stattfand]

    1994  

    Event/congress Internationales Symposium (1992.09, BirminghamEngland)
    Author's details David Hill (Hrsg.)
    Language German ; English
    Size 234 S, Ill, 23 cm
    Publisher Westdt. Verl
    Publishing place Opladen
    Document type Book ; Conference proceedings
    Note Beitr. teilw. dt., teilw. engl. ; Literaturangaben
    ISBN 3531124455 ; 9783531124452
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  8. Book ; Conference proceedings: Jakob Michael Reinhold Lenz

    Hill, David

    Studien zum Gesamtwerk ; [... Beiträge zu einem internationalen Symposium, das aus Anlaß des 200. Todestages von Jakob Michael Reinhold Lenz im September 1992 in Birmingham, England, stattfand]

    1994  

    Event/congress Internationales Symposium (1992.09, BirminghamEngland)
    Author's details David Hill (Hrsg.)
    Language German ; English
    Size 234 S, Ill, 23 cm
    Publisher Westdt. Verl
    Publishing place Opladen
    Document type Book ; Conference proceedings
    Note Beitr. teilw. dt., teilw. engl. ; Literaturangaben
    ISBN 3531124455 ; 9783531124452
    Database Former special subject collection: coastal and deep sea fishing

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  9. Article: Cyclohexenones as Michael acceptors in the Staunton-Weinreb annulation: a simple stannane modification for the synthesis of polycyclic systems.

    Hill, Bryan / Rodrigo, Russell

    Organic letters

    2005  Volume 7, Issue 23, Page(s) 5223–5225

    Abstract: ... stannane underwent a Michael addition-Dieckmann condensation sequence with various cyclohexenones ...

    Abstract [reaction: see text] o-Toluate anions generated via transmetalation from the corresponding tributyl stannane underwent a Michael addition-Dieckmann condensation sequence with various cyclohexenones. This protocol provides an efficient entry into complex polycyclic systems without the use of beta-alkoxy enones hitherto required for the reaction.
    Language English
    Publishing date 2005-11-10
    Publishing country United States
    Document type Journal Article
    ISSN 1523-7060
    ISSN 1523-7060
    DOI 10.1021/ol052058u
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: 30 Years of Cholesterol Metabolism: the Work of Michael Brown and Joseph Goldstein

    Kresge, Nicole / Simoni, Robert D / Hill, Robert L

    Journal of biological chemistry. 2006 Aug. 4, v. 281, no. 31

    2006  

    Language English
    Dates of publication 2006-0804
    Size p. e25.
    Publishing place American Society for Biochemistry and Molecular Biology
    Document type Article
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    Database NAL-Catalogue (AGRICOLA)

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