Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners

Farrell, K; Safe, L; Safe, S

doi:10.1016/0003-9861(87)90485-1

Title: Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners

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Abstract

Microchlorination of 1,4,9(/sup 3/H)dibenzofuran gave several polychlorinated dibenzofuran (PCDF) products and 2,3,7,8-(/sup 3/H)tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-(/sup 3/H)pentachlorodibenzofuran (PeCDF), and 1,2,3,6,7,8-/1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) of high specific activity (57, 34, and 32.5 Ci/mmol, respectively) were purified by preparative high-pressure liquid chromatography. These compounds were investigated as radioligands for the rat liver cytosolic aryl hydrocarbon (Ah) receptor protein. Like 2,3,7,8-(/sup 3/H)tetrachlorodibenzo-p-dioxin (TCDD), the radiolabeled PCDF congeners exhibited saturable binding with the receptor protein and sucrose density gradient analysis of the radiolabeled ligand-receptor complexes gave specific binding peaks with comparable sedimentation profiles. The rank order of radioligand binding affinities (Kd values) was 2,3,7,8-TCDD greater than 2,3,7,8-TCDF greater than 1,2,3,6,7,8-HCDF greater than 1,2,3,7,8-PeCDF and the maximum difference in Kd values for the four radioligands was less than 13-fold (0.44-5.9 nM). The interactions of the PCDF radioligands with the cytosolic receptor all exhibited saturable binding curves and linear Scatchard plots and the slopes of their Hill plots were in the range 1.0-1.1, thus indicating that cooperativity was not a factor in these binding interactions. The relative stabilities and dissociation kinetics of the radioligand-receptor complexes were highly dependent on the structure of the radioligand. The dissociation curves of the 2,3,7,8-(/sup 3/H)TCDD and PCDF receptor complexes were biphasic and thismore »« less

Authors:: Farrell, K; Safe, L; Safe, S

Publication Date:: Sun Nov 15 00:00:00 EST 1987

Research Org.:: Texas A and M Univ., College Station

OSTI Identifier:: 5601303

Resource Type:: Journal Article

Journal Name:: Arch. Biochem. Biophys.; (United States)

Additional Journal Information:: Journal Volume: 259:1

Country of Publication:: United States

Language:: English

Subject:: 63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; BENZOFURANS; CHLORINATION; CHLORINATED AROMATIC HYDROCARBONS; BIOCHEMICAL REACTION KINETICS; STRUCTURE-ACTIVITY RELATIONSHIPS; AFFINITY; LIGANDS; LIQUID COLUMN CHROMATOGRAPHY; LIVER; RATS; RECEPTORS; TRITIUM COMPOUNDS; ANIMALS; AROMATICS; BODY; CHEMICAL REACTIONS; CHROMATOGRAPHY; DIGESTIVE SYSTEM; FURANS; GLANDS; HALOGENATED AROMATIC HYDROCARBONS; HALOGENATION; HETEROCYCLIC COMPOUNDS; KINETICS; LABELLED COMPOUNDS; MAMMALS; MEMBRANE PROTEINS; ORGANIC CHLORINE COMPOUNDS; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC OXYGEN COMPOUNDS; ORGANS; PROTEINS; REACTION KINETICS; RODENTS; SEPARATION PROCESSES; VERTEBRATES; 560300* - Chemicals Metabolism & Toxicology; 550201 - Biochemistry- Tracer Techniques

Citation Formats


                    Farrell, K, Safe, L, and Safe, S. Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners.  United States: N. p., 1987. 
        Web.  doi:10.1016/0003-9861(87)90485-1.

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                    Farrell, K, Safe, L, & Safe, S. Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners.  United States.  https://doi.org/10.1016/0003-9861(87)90485-1

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                    Farrell, K, Safe, L, and Safe, S. 1987.  
        "Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners".  United States.  https://doi.org/10.1016/0003-9861(87)90485-1.

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@article{osti_5601303,

  title        = {Synthesis and aryl hydrocarbon receptor binding properties of radiolabeled polychlorinated dibenzofuran congeners},

  author       = {Farrell, K and Safe, L and Safe, S},

  abstractNote = {Microchlorination of 1,4,9(/sup 3/H)dibenzofuran gave several polychlorinated dibenzofuran (PCDF) products and 2,3,7,8-(/sup 3/H)tetrachlorodibenzofuran (TCDF), 1,2,3,7,8-(/sup 3/H)pentachlorodibenzofuran (PeCDF), and 1,2,3,6,7,8-/1,2,3,4,7,8-hexachlorodibenzofuran (HCDF) of high specific activity (57, 34, and 32.5 Ci/mmol, respectively) were purified by preparative high-pressure liquid chromatography. These compounds were investigated as radioligands for the rat liver cytosolic aryl hydrocarbon (Ah) receptor protein. Like 2,3,7,8-(/sup 3/H)tetrachlorodibenzo-p-dioxin (TCDD), the radiolabeled PCDF congeners exhibited saturable binding with the receptor protein and sucrose density gradient analysis of the radiolabeled ligand-receptor complexes gave specific binding peaks with comparable sedimentation profiles. The rank order of radioligand binding affinities (Kd values) was 2,3,7,8-TCDD greater than 2,3,7,8-TCDF greater than 1,2,3,6,7,8-HCDF greater than 1,2,3,7,8-PeCDF and the maximum difference in Kd values for the four radioligands was less than 13-fold (0.44-5.9 nM). The interactions of the PCDF radioligands with the cytosolic receptor all exhibited saturable binding curves and linear Scatchard plots and the slopes of their Hill plots were in the range 1.0-1.1, thus indicating that cooperativity was not a factor in these binding interactions. The relative stabilities and dissociation kinetics of the radioligand-receptor complexes were highly dependent on the structure of the radioligand. The dissociation curves of the 2,3,7,8-(/sup 3/H)TCDD and PCDF receptor complexes were biphasic and this suggests that there may be a temporal shift in ligand binding affinities. However, the rates of dissociation did not correlate with the rank order of ligand binding affinities.},

  doi          = {10.1016/0003-9861(87)90485-1},

  url          = {https://www.osti.gov/biblio/5601303},
  journal      = {Arch. Biochem. Biophys.; (United States)},
number       = ,

  volume       = 259:1,

  place        = {United States},

  year         = {Sun Nov 15 00:00:00 EST 1987},

  month        = {Sun Nov 15 00:00:00 EST 1987}

}

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