1 Ocak 1999 Dergi makalesi Açık Erişim

Rungeler, P; Castro, V; Mora, G; Goren, N; Vichnewski, W; Pahl, HL; Merfort, I; Schmidt, TJ

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        "name": "Rungeler, P"
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        "name": "Castro, V"
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      {
        "name": "Mora, G"
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        "name": "Vichnewski, W"
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    "description": "Many sesquiterpene lactones (SLs) possess considerable anti-inflammatory activity. They inhibit the transcription factor NF-kappa B by selectively alkylating its p65 subunit probably by reacting with cysteine residues. Here we assayed 28 sesquiterpene lactones for their ability to inhibit NF-kappa B. The majority of the potent NF-kappa B inhibitors possess two reactive centers in form of an amethylene-gamma-lactone group and an alpha,beta- or alpha,beta,gamma,delta-unsaturated carbonyl group. Based on computer molecular modelling we propose a molecular mechanism of action, which is able to explain the p65 selectivity of the SLs and the observed correlation of high activity with alkylant bifunctionality. A single bifunctional SL molecule can alkylate the cysteine residue (Cys 38) in the DNA binding loop 1 (L1) and a further cysteine (Cys 120) in the nearby E' region. This cross link alters the position of tyrosine 36 and additional amino acids in such a way that their specific interactions with the DNA become impossible. We also created a model for monofunctional SLs. (C) 1999 Elsevier Science Ltd. All rights reserved.", 
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      "issue": "11", 
      "pages": "2343-2352", 
      "title": "BIOORGANIC & MEDICINAL CHEMISTRY", 
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    "title": "Inhibition of transcription factor NF-kappa B by sesquiterpene lactones: a proposed molecular mechanism of action"
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