1 Ocak 1999 Dergi makalesi Açık Erişim

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

Dublin Core

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  <dc:creator>Rungeler, P</dc:creator>
  <dc:creator>Castro, V</dc:creator>
  <dc:creator>Mora, G</dc:creator>
  <dc:creator>Goren, N</dc:creator>
  <dc:creator>Vichnewski, W</dc:creator>
  <dc:creator>Pahl, HL</dc:creator>
  <dc:creator>Merfort, I</dc:creator>
  <dc:creator>Schmidt, TJ</dc:creator>
  <dc:date>1999-01-01</dc:date>
  <dc: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.</dc:description>
  <dc:identifier>https://aperta.ulakbim.gov.trrecord/101601</dc:identifier>
  <dc:identifier>oai:zenodo.org:101601</dc:identifier>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>http://www.opendefinition.org/licenses/cc-by</dc:rights>
  <dc:source>BIOORGANIC &amp; MEDICINAL CHEMISTRY 7(11) 2343-2352</dc:source>
  <dc:title>Inhibition of transcription factor NF-kappa B by sesquiterpene lactones: a proposed molecular mechanism of action</dc:title>
  <dc:type>info:eu-repo/semantics/article</dc:type>
  <dc:type>publication-article</dc:type>
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