Halogen bonding (XB) is an attractive interaction between a halogen atom and an electron donor. Although halogens are electron-rich atoms, they act as electrophiles in these types of interactions. This is due to the presence of a significant positive charge (σ-hole) on the halogen atoms in organic halides along the R-X (R = carbon, nitrogen, halogen) bond. With an increase in the polarizability down the group from fluorine to iodine, the positive charge on the σ-hole increases, which leads to an increase in the strength of XB. Numerous studies revealed that XB is a useful tool to develop supramolecular architectures by self-assembly. Interestingly, XBs are also observed in many biomolecules, such as protein–ligand complexes and nucleic acids containing halogenated nucleotides. In fact, XBs are extensively used to increase the potency and selectivity of small molecule ligands to a target protein. In this minireview, we discuss the role of XBs in the molecular recognition of thyroid hormones (THs) and their metabolites by various transport proteins and thyroid hormone receptors (TRs). THs are naturally occurring iodinated small molecules that are synthesized by the thyroid gland and carried to various target organs by several serum transport proteins, such as transthyretin, human serum albumin, and thyroxine-binding globulin. Interestingly, all these proteins form XBs with THs and these interactions play important roles in the high affinity binding. Furthermore, TRs, such as TRα and TRβ also form XBs with the 3-iodine of THs and triiodothyroacetic acid, an endogenous TH metabolite that shows thyromimetic activity.

中文翻译：

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运输蛋白和甲状腺激素受体对甲状腺激素及其代谢物分子识别中的卤素键合

卤素键 (XB) 是卤素原子和电子供体之间的一种有吸引力的相互作用。尽管卤素是富电子原子，但它们在这些类型的相互作用中充当亲电试剂。这是由于有机卤化物中沿 RX（R = 碳、氮、卤素）键的卤素原子上存在显着的正电荷（σ-空穴）。随着基团从氟到碘的极化率增加，σ孔上的正电荷增加，导致XB强度增加。大量研究表明，XB 是通过自组装开发超分子结构的有用工具。有趣的是，在许多生物分子中也观察到 XB，例如蛋白质-配体复合物和含有卤化核苷酸的核酸。实际上，XB 广泛用于增加小分子配体对靶蛋白的效力和选择性。在这篇小综述中，我们讨论了 XB 在各种转运蛋白和甲状腺激素受体 (TR) 对甲状腺激素 (TH) 及其代谢物的分子识别中的作用。THs 是天然存在的碘化小分子，由甲状腺合成并通过几种血清转运蛋白（例如转甲状腺素蛋白、人血清白蛋白和甲状腺素结合球蛋白）运送到各种靶器官。有趣的是，所有这些蛋白质与 THs 形成 XB，这些相互作用在高亲和力结合中起着重要作用。此外，TRs，如 TRα 和 TRβ，也与 THs 的 3-碘和三碘甲腺乙酸形成 XBs，三碘甲腺乙酸是一种内源性 TH 代谢物，具有拟甲状腺素活性。