In Vitro and in Silico Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins

• Published in: Environmental Science & Technology
• Main Authors: Hill, Katie L., Mortensen, Åse-Karen, Teclechiel, Daniel, Willmore, William G., Sylte, Ingebrigt, Jenssen, Bjørn Munro, Letcher, Robert James
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Chemical Society 2017
• Subjects: VDP::Mathematics and natural science: 400::Zoology and botany: 480; VDP::Matematikk og Naturvitenskap: 400::Zoologiske og botaniske fag: 480; Arctic
• Online Access: https://hdl.handle.net/10037/15155; https://doi.org/10.1021/acs.est.7b04617

Accepted manuscript version. Published version available at https://doi.org/10.1021/acs.est.7b04617. Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is a highly brominated additive flame retardant (FR). Debrominated photodegradates of TeDBDiPhOBz are hydroxylated in vitro in liver microsomal assays based on herring gulls ( Larus argentatus ), including one metabolite identified as 4 ″ -OH-2,2 ′ ,2 ″ ,4-tetrabromo-DiPhOBz. Chemically related methoxylated tetra- to hexabromo-DiPhOBzs are known contaminants in herring gulls. Collectively, nothing is currently known about biological effects of these polybrominated (PB) DiPhOBz-based compounds. The present study investigated the potential thyroidogenicity of 2,2 ′,2 ″,4-tetrabromo-(TB)-DiPhOBz along with its para -methoxy (MeO)- and hydroxy-(OH)-analogues, using an in vitro competitive protein binding assay with the human thyroid hormone (TH) transport proteins transthyretin (hTTR) and albumin (hALB). This model para -OH-TB-DiPhOBz was found to be capable of competing with thyroxine (T4) for the binding site on hTTR and hALB. In silico analyses were also conducted using a 3D homology model for gull TTR, to predict whether these TB-DiPhOBz-based compounds may also act as ligands for an avian TH transport protein despite evolutionary differences with hTTR. This analysis found all three TB-DiPhOBz analogues to be potential ligands for gull TTR and have similar binding efficacies to THs. Results indicate structure-related differences in binding affinities of these ligands and suggest there is potential for these contaminants to interact with both mammalian and avian thyroid function.