Structure-directed screening and analysis of thyroid-disrupting chemicals targeting transthyretin based on molecular recognition and chromatographic separation.

Exposure to thyroid-disrupting chemicals (TDCs) poses a great threat to human health. However, the screening and analysis of TDCs in environmental samples remain a tough work. In this study, we reported a structure-directed strategy for analysing TDCs targeting transthyretin (TTR) based on molecular imprinting and chromatographic separation. The imprinted composites were prepared using L-thyroxine (T4) as a template and a tryptophan-like monomer screened from the amino acid library. The imprinted composites exhibited an adsorption capacity of 22.2 micromol g-1 for T4 and an imprinting factor of 2.1. Chromatographic testing was then conducted among 72 chemicals using the imprinted composites-packed column. High retention factors were observed for chemicals that were structurally similar to T4. The chromatographic results were compared with a dataset of 45 chemicals with known activities towards TTR. The results suggested that chemicals can be distinguished as TTR binders and non-binders by retention factors, with a predictive accuracy of more than 90%. Moreover, the retention factors of chemicals were highly correlated with the reported relative potencies obtained from TTR assays. Thus, screening of TTR-binding chemicals can be realized through this simple chromatographic method. The imprinted composites were applied for target analysis and non-target analysis of TTR-binding chemicals in dust samples. Three new TTR binders were successfully identified and verified by this method. The combination of molecular imprinting and chromatography opens up a new approach for screening TDCs targeting TTR.