Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/124711
Title: Interaction of mesalasine (5-ASA) with translational initiation factors eIF4 partially explains 5-ASA anti-inflammatory and anti-neoplastic activities
Authors: Lyakhovich, A. 
Michlmayr, A.
Bakulina, A.
Gerner, C.
Oehler, R.
Gasche, C.
Keywords: 2D-DIGE
5-ASA
Chemogenomics
IBD
Mesalazine
OMICs
Issue Date: Mar-2011
Citation: Lyakhovich, A.,Michlmayr, A.,Bakulina, A.,Gerner, C.,Oehler, R.,Gasche, C. (2011-03). Interaction of mesalasine (5-ASA) with translational initiation factors eIF4 partially explains 5-ASA anti-inflammatory and anti-neoplastic activities. Medicinal Chemistry 7 (2) : 92-98. ScholarBank@NUS Repository.
Abstract: 5-aminosalicylic acid (5-ASA or mesalazine) is widely used for treatment of inflammatory bowel disease and considered to be cancer preventive. Still, the molecular mechanisms explaining its properties remain largely unknown, partially due to the lack of instrumentarium needed to identify its array of molecular targets. Modern OMICs-based technologies utilized in this study may serve as a powerful and unbiased tool to search for such targets. Here we demonstrate that 5-ASA alters β-catenin immunocomplex formation by changing complex binding of seven proteins including translation initiation factors eIF4b. OMICs-based cross-testing by reverse in-gel chemogenomics (utilizing 5-ASA's fluorescent properties), in-silico docking and surface plasmon resonance experiments identified binding of 5-ASA to eIF4e's capbinding pocket, a key regulatory site for protein synthesis. In-vitro translation experiments with rabbit reticulocytes confirmed a dose-dependent inhibition of protein syntheses by 5-ASA. By using two unbiased and independent OMICs-based experimental approaches two members of the cellular translation machinery, eIF4b and IF4e, were identified as targets of 5-ASA. Inhibition of protein syntheses is a previously unrecognized property of 5-ASA that may add to its antiinflammatory and anti-neoplastic activities. © 2011 Bentham Science Publishers Ltd.
Source Title: Medicinal Chemistry
URI: http://scholarbank.nus.edu.sg/handle/10635/124711
ISSN: 15734064
Appears in Collections:Staff Publications

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