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发表时间：2022-10-10

发表刊物：科学通报

卷号：59

期号：27

页面范围：2673-2680

ISSN号：0023-074X

摘要：Thyroid disrupting chemicals (TDCs) can compete for the binding sites of
   transport proteins with thyroid hormones (THs) and alter the homeostasis
   of THs. The halogen moieties in TDCs play key role in determining the
   interactions between TDCs and transthyretin (TTR). Herein, the effects
   of halogenation on the binding interaction was investigated by analyzing
   the TTR crystal structures, the TDCs-TTR complex from molecular
   simulation, and the relative competing potency of a chemical with T_4
   binding to hTTR (logRP).We found that the halogen moieties in TDCs can
   affect the binding interactions by forming halogen bonds and
   halogen-hydrogen bonds with TTR and through inductive effects and
   hydrophobic effects. The halogen bonds (mainly halogen-oxygen bonds) and
   halogen-hydrogen bonds enhance the binding between organic halogenated
   compounds and TTR. Besides, for the halogenated phenolic compounds, the
   inductive effect is a main factor determining the logRP values. The
   hydrophobic effect is a critical factor governing the interactions
   between non-ionizable compounds (e.g. polybrominated diphenyl ethers)
   and TTR.

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