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Inhibitory activity of polyhydroxycarboxylate chelators against recombinant NF-kappaB p50 protein-DNA binding |
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| Authors: | Sharma Rakesh K Pande Vineet Ramos Maria J Rajor Hament K Chopra Shilpa Meguro Kazuyuki Inoue Jun-ichiro Otsuka Masami |
| Institution: | a Department of Chemistry, University of Delhi, Delhi 7, India b CEQUP/Departamento de Química, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal c Institute of Medical Science, University of Tokyo, Shirokane-dai, Minato-ku, Tokyo 108-0071, Japan d Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 5-1 Oehonmachi, Kumamoto 862-0973, Japan |
| Abstract: | The inhibitory effect of 7,8-dihydroxy-4-methylcoumarin (7,8-DHMC), 5,7-dihydroxy-4-methylcoumarin (5,7-DHMC), and gallic acid on the DNA binding of recombinant p50 protein and their interaction with zinc ion were studied. Electrophoretic mobility shift assay (EMSA) using p50 and biotin labeled DNA has shown that gallic acid is more effective than the dihydroxycoumarins in inhibiting the p50-DNA binding. Molecular modeling studies suggest an explanation for these observations. Effect of the addition of zinc after p50-DNA-binding inhibition by gallic acid was also studied. Chemical speciation and formation constant studies show that gallic acid forms a more stable 1:1 complex with zinc ion in comparison to the dihydroxycoumarins. |
| Keywords: | NF-κB inhibitors 7 8-Dihydroxy-4-methylcoumarin 5 7-Dihydroxy-4-methylcoumarin Gallic acid p50 protein |
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