TY - JOUR
T1 - A new structure-affinity relationship for TCDD receptor binding
AU - Gillner, Mikael
AU - Fernström, Birgitta
AU - Gustafsson, Jan Åke
AU - Bergman, Jan
AU - Cambillau, Christian
N1 - Funding Information:
ACKNOWLEDGEMENTS This research was supported by the Bank of Sweden Tercentenary Foundation, the Foundation, the Funds of the Karollnska Institute, the Swedish Cancer Society, Swedish Council for Coordination and Planning of Research.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1986
Y1 - 1986
N2 - 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.
AB - 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.
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U2 - 10.1016/0045-6535(86)90453-4
DO - 10.1016/0045-6535(86)90453-4
M3 - Article
AN - SCOPUS:0022870624
SN - 0045-6535
VL - 15
SP - 1673
EP - 1680
JO - Chemosphere
JF - Chemosphere
IS - 9-12
ER -