A new structure-affinity relationship for TCDD receptor binding

Mikael Gillner, Birgitta Fernström, Jan Åke Gustafsson, Jan Bergman, Christian Cambillau

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

We have investigated the capacity of various indoles to inhibit specific binding of [1,6-3H]2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD) in rat liver cytosol, as analyzed by electrofocusing in polyacrylamide gels. Of these indoles, indolo[3,2-b]carbazole was the most active. The IC50 value for TCDD receptor binding of indolo[3,2-b]carbazole as well as for 2,3,7,8-tetrachlorodibenzofuran was 3.6 nM. We have also studied the influence on binding exerted by introduction of some substituents on indolo[3,2-b]carbazole. Substitution with methyl groups at the 5 and 11 positions resulted in an increased affinity (IC50 1.2 nM) for the TCDD receptor as compared to the parent compound. Computer-supported molecular structure studies indicated that if the van der Waals radii of atoms are included, a rectangle of 6.8 × 13.7 Å may account for the binding of high-affinity ligands to the TCDD receptor.

Original languageEnglish (US)
Pages (from-to)1673-1680
Number of pages8
JournalChemosphere
Volume15
Issue number9-12
DOIs
StatePublished - 1986

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

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