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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{
  "URL": "https://aperta.ulakbim.gov.tr/record/101601", 
  "abstract": "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.", 
  "author": [
    {
      "family": "Rungeler", 
      "given": " P"
    }, 
    {
      "family": "Castro", 
      "given": " V"
    }, 
    {
      "family": "Mora", 
      "given": " G"
    }, 
    {
      "family": "Goren", 
      "given": " N"
    }, 
    {
      "family": "Vichnewski", 
      "given": " W"
    }, 
    {
      "family": "Pahl", 
      "given": " HL"
    }, 
    {
      "family": "Merfort", 
      "given": " I"
    }, 
    {
      "family": "Schmidt", 
      "given": " TJ"
    }
  ], 
  "container_title": "BIOORGANIC & MEDICINAL CHEMISTRY", 
  "id": "101601", 
  "issue": "11", 
  "issued": {
    "date-parts": [
      [
        1999, 
        1, 
        1
      ]
    ]
  }, 
  "page": "2343-2352", 
  "title": "Inhibition of transcription factor NF-kappa B by sesquiterpene lactones: a proposed molecular mechanism of action", 
  "type": "article-journal", 
  "volume": "7"
}