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  1. Article: A genetically-encoded fluorescent biosensor for visualization of acetyl-CoA in live cells.

    Smith, Joseph J / Valentino, Taylor R / Ablicki, Austin H / Banerjee, Riddhidev / Colligan, Adam R / Eckert, Debra M / Desjardins, Gabrielle A / Diehl, Katharine L

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Acetyl-coenzyme A is a central metabolite that participates in many cellular pathways. Evidence suggests that acetyl-CoA production and consumption are highly compartmentalized in mammalian cells. Yet methods to measure acetyl-CoA in living cells are ... ...

    Abstract Acetyl-coenzyme A is a central metabolite that participates in many cellular pathways. Evidence suggests that acetyl-CoA production and consumption are highly compartmentalized in mammalian cells. Yet methods to measure acetyl-CoA in living cells are lacking. In this work, we engineer an acetyl-CoA biosensor from the bacterial protein PanZ and circularly permuted green fluorescent protein (cpGFP). We biochemically characterize the sensor and demonstrate its selectivity for acetyl-CoA over other CoA species. We then deploy the biosensor in E. coli and HeLa cells to demonstrate its utility in living cells. In E. coli, we show that the biosensor enables detection of rapid changes in acetyl-CoA levels. In human cells, we show that the biosensor enables subcellular detection and reveals the compartmentalization of acetyl-CoA metabolism.
    Language English
    Publishing date 2024-02-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.31.573774
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Potential SARS-CoV-2 main protease inhibitors.

    Banerjee, Riddhidev / Perera, Lalith / Tillekeratne, L M Viranga

    Drug discovery today

    2020  Volume 26, Issue 3, Page(s) 804–816

    Abstract: The coronavirus disease 2019 (COVID-19) pandemic has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but new drug candidates ... ...

    Abstract The coronavirus disease 2019 (COVID-19) pandemic has prompted an urgent need for new treatment strategies. No target-specific drugs are currently available for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but new drug candidates targeting the viral replication cycle are being explored. A prime target of drug-discovery efforts is the SARS-CoV-2 main protease (M
    MeSH term(s) COVID-19/drug therapy ; Coronavirus 3C Proteases/antagonists & inhibitors ; Coronavirus 3C Proteases/chemistry ; Coronavirus 3C Proteases/metabolism ; Drug Design ; Drug Discovery/methods ; Humans ; SARS-CoV-2/drug effects ; SARS-CoV-2/physiology ; Virus Replication/drug effects
    Chemical Substances Coronavirus 3C Proteases (EC 3.4.22.28)
    Language English
    Publishing date 2020-12-09
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
    ZDB-ID 1324988-5
    ISSN 1878-5832 ; 1359-6446
    ISSN (online) 1878-5832
    ISSN 1359-6446
    DOI 10.1016/j.drudis.2020.12.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Rational design of metabolically stable HDAC inhibitors: An overhaul of trifluoromethyl ketones.

    Riddhidev, Banerjee / Endri, Karaj / Sabitri, Lamichhane / Kotsull Lauren, N / Nishanth, Kuganesan / Dragan, Isailovic / Mary Kay H, Pflum / James, Slama / William, Taylor / L M Viranga, Tillekeratne

    European journal of medicinal chemistry

    2022  Volume 244, Page(s) 114807

    Abstract: Epigenetic regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to ... ...

    Abstract Epigenetic regulation of gene expression using histone deacetylase (HDAC) inhibitors is a promising strategy for developing new anticancer agents. The most common HDAC inhibitors are hydroxamates, which, though highly potent, have limitations due to their poor pharmacokinetic properties and lack of isoform selectivity. Trifluoromethylketones (TFMK) developed as alternatives to hydroxamates are rapidly metabolized to inactive trifluoromethyl alcohols in vivo, which prevented their further development as potential drug candidates. In order to overcome this limitation, we designed trifluoropyruvamides (TFPAs) as TFMK surrogates. The presence of an additional electron withdrawing group next to the ketone carbonyl group made the hydrate form of the ketone more stable, thus preventing its metabolic reduction to alcohol in vivo. In addition, this structural modification reduces the potential of the TFMK group to act as a covalent warhead to eliminate off-target effects. Additional structural changes in the cap group of the inhibitors gave analogues with IC
    MeSH term(s) Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylase Inhibitors/chemistry ; Ketones/pharmacology ; Epigenesis, Genetic ; Repressor Proteins/metabolism ; Hydroxamic Acids/chemistry ; Protein Isoforms/metabolism
    Chemical Substances Histone Deacetylase Inhibitors ; Ketones ; Repressor Proteins ; Hydroxamic Acids ; Protein Isoforms
    Language English
    Publishing date 2022-10-05
    Publishing country France
    Document type Journal Article
    ZDB-ID 188597-2
    ISSN 1768-3254 ; 0009-4374 ; 0223-5234
    ISSN (online) 1768-3254
    ISSN 0009-4374 ; 0223-5234
    DOI 10.1016/j.ejmech.2022.114807
    Database MEDical Literature Analysis and Retrieval System OnLINE

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