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  1. Article ; Online: Discovery of Anti-SARS-CoV-2 Nsp9 Binders from Natural Products by a Native Mass Spectrometry Approach.

    Quinn, Ronald J / Mak, Tin / Littler, Dene R / Rossjohn, Jamie / Liu, Miaomiao

    Journal of natural products

    2023  Volume 86, Issue 12, Page(s) 2630–2637

    Abstract: The search for effective antiviral agents against SARS-CoV-2 remains a critical global endeavor. In this study, we focused on the viral nucleocapsid protein Nsp9, which is a key player in viral RNA replication and an attractive drug target. Employing a ... ...

    Abstract The search for effective antiviral agents against SARS-CoV-2 remains a critical global endeavor. In this study, we focused on the viral nucleocapsid protein Nsp9, which is a key player in viral RNA replication and an attractive drug target. Employing a two-pronged approach, an in-house natural product library was screened using native mass spectrometry to identify compounds capable of binding to Nsp9. From the initial screening, apart from the previously reported hit oridonin (protein binding ratio of 0.56 in the initial screening,
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19 ; Diterpenes, Kaurane/pharmacology ; Protein Binding ; Antiviral Agents/pharmacology
    Chemical Substances oridonin (0APJ98UCLQ) ; Diterpenes, Kaurane ; Antiviral Agents
    Language English
    Publishing date 2023-11-22
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 304325-3
    ISSN 1520-6025 ; 0163-3864
    ISSN (online) 1520-6025
    ISSN 0163-3864
    DOI 10.1021/acs.jnatprod.3c00636
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1144: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Collision-Induced Affinity Selection Mass Spectrometry for Identification of Ligands.

    Mak, Tin / Rossjohn, Jamie / Littler, Dene R / Liu, Miaomiao / Quinn, Ronald J

    ACS bio & med chem Au

    2022  Volume 2, Issue 5, Page(s) 450–455

    Abstract: Hyphenated mass spectrometry has been used to identify ligands binding to proteins. It involves mixing protein and compounds, separation of protein-ligand complexes from unbound compounds, dissociation of the protein-ligand complex, separation to remove ... ...

    Abstract Hyphenated mass spectrometry has been used to identify ligands binding to proteins. It involves mixing protein and compounds, separation of protein-ligand complexes from unbound compounds, dissociation of the protein-ligand complex, separation to remove protein, and injection of the supernatant into a mass spectrometer to observe the ligand. Here we report collision-induced affinity selection mass spectrometry (CIAS-MS), which allows separation and dissociation inside the instrument. The quadrupole was used to select the ligand-protein complex and allow unbound molecules to be exhausted to vacuum. Collision-induced dissociation (CID) dissociated the protein-ligand complex, and the ion guide and resonance frequency were used to selectively detect the ligand. A known SARS-CoV-2 Nsp9 ligand, oridonin, was successfully detected when it was mixed with Nsp9. We provide proof-of-concept data that the CIAS-MS method can be used to identify binding ligands for any purified protein.
    Language English
    Publishing date 2022-05-18
    Publishing country United States
    Document type Journal Article
    ISSN 2694-2437
    ISSN (online) 2694-2437
    DOI 10.1021/acsbiomedchemau.2c00021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Development of an HPLC-based guanosine monophosphate kinase assay and application to Plasmodium vivax guanylate kinase

    Pedro, Liliana / Cross, Megan / Hofmann, Andreas / Mak, Tin / Quinn, Ronald J

    Analytical biochemistry. 2019 June 15, v. 575

    2019  

    Abstract: The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic ... ...

    Abstract The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic reaction (GMP, ATP, ADP and GDP) to unambiguously determine percent conversion of substrate into product. It uses a commercially available C18 column which can separate reaction samples by elution under isocratic conditions in 12 min per run. The kinetics of the forward reaction catalyzed by Plasmodium vivax guanylate kinase (PvGK), a potential drug target against malaria, was determined. The relative concentrations of the two substrates (GMP and ATP) have a distinct effect on reaction velocity. Kinetic analyses showed the PvGK-catalyzed reaction to be associated with atypical kinetics, where substrate inhibition kinetics and non-Michaelis-Menten (sigmoidal) kinetics were found with respect to GMP and ATP, respectively. Additionally, the method was used in inhibition assays to screen twenty fragment-like compounds. The assays were robust and reproducible, with a signal window of 3.8 and a Z’ factor of 0.6. For the best inhibitor, an IC50 curve was generated.
    Keywords Plasmodium vivax ; absorption ; adenosine diphosphate ; adenosine triphosphate ; drugs ; enzymatic reactions ; enzyme activity ; enzymes ; guanosine monophosphate ; high performance liquid chromatography ; inhibitory concentration 50 ; malaria
    Language English
    Dates of publication 2019-0615
    Size p. 63-69.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2019.03.022
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 70/124: Show issues

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  4. Article ; Online: Development of an HPLC-based guanosine monophosphate kinase assay and application to Plasmodium vivax guanylate kinase.

    Pedro, Liliana / Cross, Megan / Hofmann, Andreas / Mak, Tin / Quinn, Ronald J

    Analytical biochemistry

    2019  Volume 575, Page(s) 63–69

    Abstract: The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic ... ...

    Abstract The development of a high-performance liquid chromatography (HPLC)-based method, for guanosine monophosphate kinase activity assays, is presented. The method uses the intrinsic UV absorption (at 260 nm) of substrates and products of the enzymatic reaction (GMP, ATP, ADP and GDP) to unambiguously determine percent conversion of substrate into product. It uses a commercially available C18 column which can separate reaction samples by elution under isocratic conditions in 12 min per run. The kinetics of the forward reaction catalyzed by Plasmodium vivax guanylate kinase (PvGK), a potential drug target against malaria, was determined. The relative concentrations of the two substrates (GMP and ATP) have a distinct effect on reaction velocity. Kinetic analyses showed the PvGK-catalyzed reaction to be associated with atypical kinetics, where substrate inhibition kinetics and non-Michaelis-Menten (sigmoidal) kinetics were found with respect to GMP and ATP, respectively. Additionally, the method was used in inhibition assays to screen twenty fragment-like compounds. The assays were robust and reproducible, with a signal window of 3.8 and a Z' factor of 0.6. For the best inhibitor, an IC
    MeSH term(s) Animals ; Catalysis ; Chromatography, High Pressure Liquid/methods ; Guanylate Kinases/metabolism ; Kinetics ; Phosphorylation ; Plasmodium vivax/enzymology
    Chemical Substances Guanylate Kinases (EC 2.7.4.8)
    Language English
    Publishing date 2019-03-31
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1110-1
    ISSN 1096-0309 ; 0003-2697
    ISSN (online) 1096-0309
    ISSN 0003-2697
    DOI 10.1016/j.ab.2019.03.022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 389: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  5. Article ; Online: A Phenotarget Approach for Identifying an Alkaloid Interacting with the Tuberculosis Protein Rv1466.

    Xie, Yan / Feng, Yunjiang / Di Capua, Angela / Mak, Tin / Buchko, Garry W / Myler, Peter J / Liu, Miaomiao / Quinn, Ronald J

    Marine drugs

    2020  Volume 18, Issue 3

    Abstract: In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods ... ...

    Abstract In recent years, there has been a revival of interest in phenotypic-based drug discovery (PDD) due to target-based drug discovery (TDD) falling below expectations. Both PDD and TDD have their unique advantages and should be used as complementary methods in drug discovery. The PhenoTarget approach combines the strengths of the PDD and TDD approaches. Phenotypic screening is conducted initially to detect cellular active components and the hits are then screened against a panel of putative targets. This PhenoTarget protocol can be equally applied to pure compound libraries as well as natural product fractions. Here we described the use of the PhenoTarget approach to identify an anti-tuberculosis lead compound. Fractions from
    MeSH term(s) Alkaloids/chemistry ; Alkaloids/pharmacology ; Antitubercular Agents/chemistry ; Antitubercular Agents/pharmacology ; Drug Delivery Systems ; Drug Discovery/methods ; Drug Evaluation, Preclinical ; High-Throughput Screening Assays ; Humans ; Molecular Weight ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Phenotype ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Proteome/drug effects
    Chemical Substances Alkaloids ; Antitubercular Agents ; Plant Extracts ; Proteome
    Language English
    Publishing date 2020-03-05
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175190-0
    ISSN 1660-3397 ; 1660-3397
    ISSN (online) 1660-3397
    ISSN 1660-3397
    DOI 10.3390/md18030149
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Discovery of a Natural Product That Binds to the

    Elnaas, Ali R / Grice, Darren / Han, Jianying / Feng, Yunjiang / Capua, Angela Di / Mak, Tin / Laureanti, Joseph A / Buchko, Garry W / Myler, Peter J / Cook, Gregory / Quinn, Ronald J / Liu, Miaomiao

    Molecules (Basel, Switzerland)

    2020  Volume 25, Issue 10

    Abstract: Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over ... ...

    Abstract Elucidation of the mechanism of action of compounds with cellular bioactivity is important for progressing compounds into future drug development. In recent years, phenotype-based drug discovery has become the dominant approach to drug discovery over target-based drug discovery, which relies on the knowledge of a specific drug target of a disease. Still, when targeting an infectious disease via a high throughput phenotypic assay it is highly advantageous to identifying the compound's cellular activity. A fraction derived from the plant
    MeSH term(s) Antitubercular Agents/chemistry ; Antitubercular Agents/pharmacology ; Bacterial Proteins/antagonists & inhibitors ; Biological Products/chemistry ; Biological Products/pharmacology ; Drug Discovery ; Humans ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/pathogenicity ; Plant Extracts/chemistry ; Plant Extracts/pharmacology ; Polyalthia/chemistry ; Proteome/genetics ; Tuberculosis/drug therapy ; Tuberculosis/microbiology
    Chemical Substances Antitubercular Agents ; Bacterial Proteins ; Biological Products ; Plant Extracts ; Proteome
    Language English
    Publishing date 2020-05-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules25102384
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  7. Article ; Online: Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

    Vu, Hoan / Pedro, Liliana / Mak, Tin / McCormick, Brendan / Rowley, Jessica / Liu, Miaomiao / Di Capua, Angela / Williams-Noonan, Billy / Pham, Ngoc B / Pouwer, Rebecca / Nguyen, Bao / Andrews, Katherine T / Skinner-Adams, Tina / Kim, Jessica / Hol, Wim G J / Hui, Raymond / Crowther, Gregory J / Van Voorhis, Wesley C / Quinn, Ronald J

    ACS infectious diseases

    2018  Volume 4, Issue 4, Page(s) 431–444

    Abstract: Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in ... ...

    Abstract Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.
    MeSH term(s) Antimalarials/isolation & purification ; Antimalarials/pharmacology ; Biological Products/isolation & purification ; Biological Products/pharmacology ; Drug Evaluation, Preclinical/methods ; Mass Spectrometry/methods ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/growth & development ; Protein Binding ; Protozoan Proteins/metabolism
    Chemical Substances Antimalarials ; Biological Products ; Protozoan Proteins
    Language English
    Publishing date 2018-03-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2373-8227
    ISSN (online) 2373-8227
    DOI 10.1021/acsinfecdis.7b00197
    Database MEDical Literature Analysis and Retrieval System OnLINE

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